Viruses

23 pages, 1100 KiB

Open AccessCommunication

Phage Therapy in Germany—Update 2023

by Christian Willy, Joachim J. Bugert, Annika Y. Classen, Li Deng, Anja Düchting, Justus Gross, Jens A. Hammerl, Imke H. E. Korf, Christian Kühn, Simone Lieberknecht-Jouy, Christine Rohde, Markus Rupp, Maria J. G. T. Vehreschild, Kilian Vogele, Sarah Wienecke, Martin Witzenrath, Silvia Würstle, Holger Ziehr, Karin Moelling and Felix Broecker

Viruses 2023, 15(2), 588; https://doi.org/10.3390/v15020588 - 20 Feb 2023

Cited by 14 | Viewed by 7244

Abstract

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed [...] Read more.

Bacteriophage therapy holds promise in addressing the antibiotic-resistance crisis, globally and in Germany. Here, we provide an overview of the current situation (2023) of applied phage therapy and supporting research in Germany. The authors, an interdisciplinary group working on patient-focused bacteriophage research, addressed phage production, phage banks, susceptibility testing, clinical application, ongoing translational research, the regulatory situation, and the network structure in Germany. They identified critical shortcomings including the lack of clinical trials, a paucity of appropriate regulation and a shortage of phages for clinical use. Phage therapy is currently being applied to a limited number of patients as individual treatment trials. There is presently only one site in Germany for large-scale good-manufacturing-practice (GMP) phage production, and one clinic carrying out permission-free production of medicinal products. Several phage banks exist, but due to varying institutional policies, exchange among them is limited. The number of phage research projects has remarkably increased in recent years, some of which are part of structured networks. There is a demand for the expansion of production capacities with defined quality standards, a structured registry of all treated patients and clear therapeutic guidelines. Furthermore, the medical field is still poorly informed about phage therapy. The current status of non-approval, however, may also be regarded as advantageous, as insufficiently restricted use of phage therapy without adequate scientific evidence for effectiveness and safety must be prevented. In close coordination with the regulatory authorities, it seems sensible to first allow some centers to treat patients following the Belgian model. There is an urgent need for targeted networking and funding, particularly of translational research, to help advance the clinical application of phages. Full article

(This article belongs to the Special Issue State-of-the-Art Phage Therapy Development in Europe 2022)

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15 pages, 349 KiB

Open AccessReview

Bioinformatic Tools for NGS-Based Metagenomics to Improve the Clinical Diagnosis of Emerging, Re-Emerging and New Viruses

by Marta Ibañez-Lligoña, Sergi Colomer-Castell, Alejandra González-Sánchez, Josep Gregori, Carolina Campos, Damir Garcia-Cehic, Cristina Andrés, Maria Piñana, Tomàs Pumarola, Francisco Rodríguez-Frias, Andrés Antón and Josep Quer

Viruses 2023, 15(2), 587; https://doi.org/10.3390/v15020587 - 20 Feb 2023

Cited by 12 | Viewed by 5114

Abstract

Epidemics and pandemics have occurred since the beginning of time, resulting in millions of deaths. Many such disease outbreaks are caused by viruses. Some viruses, particularly RNA viruses, are characterized by their high genetic variability, and this can affect certain phenotypic features: tropism, [...] Read more.

Epidemics and pandemics have occurred since the beginning of time, resulting in millions of deaths. Many such disease outbreaks are caused by viruses. Some viruses, particularly RNA viruses, are characterized by their high genetic variability, and this can affect certain phenotypic features: tropism, antigenicity, and susceptibility to antiviral drugs, vaccines, and the host immune response. The best strategy to face the emergence of new infectious genomes is prompt identification. However, currently available diagnostic tests are often limited for detecting new agents. High-throughput next-generation sequencing technologies based on metagenomics may be the solution to detect new infectious genomes and properly diagnose certain diseases. Metagenomic techniques enable the identification and characterization of disease-causing agents, but they require a large amount of genetic material and involve complex bioinformatic analyses. A wide variety of analytical tools can be used in the quality control and pre-processing of metagenomic data, filtering of untargeted sequences, assembly and quality control of reads, and taxonomic profiling of sequences to identify new viruses and ones that have been sequenced and uploaded to dedicated databases. Although there have been huge advances in the field of metagenomics, there is still a lack of consensus about which of the various approaches should be used for specific data analysis tasks. In this review, we provide some background on the study of viral infections, describe the contribution of metagenomics to this field, and place special emphasis on the bioinformatic tools (with their capabilities and limitations) available for use in metagenomic analyses of viral pathogens. Full article

(This article belongs to the Special Issue Applications of Next-Generation Sequencing in Virus Discovery 2.0)

24 pages, 5060 KiB

Open AccessArticle

A Novel Mathematical Model That Predicts the Protection Time of SARS-CoV-2 Antibodies

by Zhaobin Xu, Dongqing Wei, Hongmei Zhang and Jacques Demongeot

Viruses 2023, 15(2), 586; https://doi.org/10.3390/v15020586 - 20 Feb 2023

Cited by 7 | Viewed by 2324

Abstract

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on [...] Read more.

Infectious diseases such as SARS-CoV-2 pose a considerable threat to public health. Constructing a reliable mathematical model helps us quantitatively explain the kinetic characteristics of antibody-virus interactions. A novel and robust model is developed to integrate antibody dynamics with virus dynamics based on a comprehensive understanding of immunology principles. This model explicitly formulizes the pernicious effect of the antibody, together with a positive feedback stimulation of the virus–antibody complex on the antibody regeneration. Besides providing quantitative insights into antibody and virus dynamics, it demonstrates good adaptivity in recapturing the virus-antibody interaction. It is proposed that the environmental antigenic substances help maintain the memory cell level and the corresponding neutralizing antibodies secreted by those memory cells. A broader application is also visualized in predicting the antibody protection time caused by a natural infection. Suitable binding antibodies and the presence of massive environmental antigenic substances would prolong the protection time against breakthrough infection. The model also displays excellent fitness and provides good explanations for antibody selection, antibody interference, and self-reinfection. It helps elucidate how our immune system efficiently develops neutralizing antibodies with good binding kinetics. It provides a reasonable explanation for the lower SARS-CoV-2 mortality in the population that was vaccinated with other vaccines. It is inferred that the best strategy for prolonging the vaccine protection time is not repeated inoculation but a directed induction of fast-binding antibodies. Eventually, this model will inform the future construction of an optimal mathematical model and help us fight against those infectious diseases. Full article

(This article belongs to the Special Issue RNA Viruses and Antibody Response)

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13 pages, 1587 KiB

Open AccessArticle

Dynamics of Early Establishment of SARS-CoV-2 VOC Omicron Lineages in Minas Gerais, Brazil

by Mariane Talon de Menezes, Filipe Romero Rebello Moreira, Charles Whittaker, Franciele Martins Santos, Daniel Costa Queiroz, Victor Geddes, Paula Luize Camargos Fonseca, Jaqueline Góes de Jesus, Franciane Mendes-Oliveira, Valquíria Reis-Souza, Bibiana Santos, Danielle Alves Gomes Zauli, Aline Brito de Lima, Cristiane de Brito Mendonça, Luige Biciati Alvim, Joice do Prado Silva, Frederico Scott Varella Malta, Alessandro Clayton de Souza Ferreira, Nuno R. Faria, Ester Cerdeira Sabino and Renato Santana Aguiar Show full author list Hide full author list

Viruses 2023, 15(2), 585; https://doi.org/10.3390/v15020585 - 20 Feb 2023

Cited by 4 | Viewed by 2729

Abstract

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for [...] Read more.

Brazil is one of the nations most affected by Coronavirus disease 2019 (COVID-19). The introduction and establishment of new virus variants can be related to an increase in cases and fatalities. The emergence of Omicron, the most modified SARS-CoV-2 variant, caused alarm for the public health of Brazil. In this study, we examined the effects of the Omicron introduction in Minas Gerais (MG), the second-most populous state of Brazil. A total of 430 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples from November 2021 to June 2022 from Belo Horizonte (BH) city were sequenced. These newly sequenced genomes comprise 72% of all previously available SARS-CoV-2 genomes for the city. Evolutionary analysis of novel viral genomes reveals that a great diversity of Omicron sublineages have circulated in BH, a pattern in-keeping with observations across Brazil more generally. Bayesian phylogeographic reconstructions indicate that this diversity is a product of a large number of international and national importations. As observed previously, São Paulo state is shown as a significant hub for viral spread throughout the country, contributing to around 70% of all viral Omicron introductions detected in MG. Full article

(This article belongs to the Special Issue Coronavirus Genome Evolution, Recombination and Phylogeny)

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11 pages, 1919 KiB

Open AccessBrief Report

Epitope Coverage of Anti-SARS-CoV-2 Nucleocapsid IgA and IgG Antibodies Correlates with Protection against Re-Infection by New Variants in Subsequent Waves of the COVID-19 Pandemic

by Michelle O. Mullins, Muneerah Smith, Hazel Maboreke, Andrew J. M. Nel, Ntobeko A. B. Ntusi, Wendy A. Burgers and Jonathan M. Blackburn

Viruses 2023, 15(2), 584; https://doi.org/10.3390/v15020584 - 20 Feb 2023

Cited by 1 | Viewed by 1822

Abstract

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here, [...] Read more.

The COVID-19 pandemic continues to affect individuals across the globe, with some individuals experiencing more severe disease than others. The relatively high frequency of re-infections and breakthrough infections observed with SARS-CoV-2 highlights the importance of extending our understanding of immunity to COVID-19. Here, we aim to shed light on the importance of antibody titres and epitope utilization in protection from re-infection. Health care workers are highly exposed to SARS-CoV-2 and are therefore also more likely to become re-infected. We utilized quantitative, multi-antigen, multi-epitope SARS-CoV-2 protein microarrays to measure IgG and IgA titres against various domains of the nucleocapsid and spike proteins. Potential re-infections in a large, diverse health care worker cohort (N = 300) during the second wave of the pandemic were identified by assessing the IgG anti-N titres before and after the second wave. We assessed epitope coverage and antibody titres between the ‘single infection’ and ‘re-infection’ groups. Clear differences were observed in the breadth of the anti-N response before the second wave, with the epitope coverage for both IgG (p = 0.019) and IgA (p = 0.015) being significantly increased in those who did not become re-infected compared to those who did. Additionally, the IgG anti-N (p = 0.004) and anti-S titres (p = 0.018) were significantly higher in those not re-infected. These results highlight the importance of the breadth of elicited antibody epitope coverage following natural infection in protection from re-infection and disease in the COVID-19 pandemic. Full article

(This article belongs to the Section SARS-CoV-2 and COVID-19)

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16 pages, 4585 KiB

Open AccessArticle

Whole-Genome Analysis of Influenza A(H3N2) and B/Victoria Viruses Detected in Myanmar during the COVID-19 Pandemic in 2021

by Irina Chon, Reiko Saito, Yadanar Kyaw, Moe Myat Aye, Swe Setk, Wint Wint Phyu, Keita Wagatsuma, Jiaming Li, Yuyang Sun, Teruhime Otoguro, Su Mon Kyaw Win, Sayaka Yoshioka, Nay Chi Win, Lasham Di Ja, Htay Htay Tin and Hisami Watanabe

Viruses 2023, 15(2), 583; https://doi.org/10.3390/v15020583 - 20 Feb 2023

Cited by 4 | Viewed by 3190

Abstract

An influenza circulation was observed in Myanmar between October and November in 2021. Patients with symptoms of influenza-like illness were screened using rapid diagnostic test (RDT) kits, and 147/414 (35.5%) upper respiratory tract specimens presented positive results. All RDT-positive samples were screened by [...] Read more.

An influenza circulation was observed in Myanmar between October and November in 2021. Patients with symptoms of influenza-like illness were screened using rapid diagnostic test (RDT) kits, and 147/414 (35.5%) upper respiratory tract specimens presented positive results. All RDT-positive samples were screened by a commercial multiplex real-time polymerase chain reaction (RT-PCR) assay, and 30 samples positive for influenza A(H3N2) or B underwent further typing/subtyping for cycle threshold (Ct) value determination based on cycling probe RT-PCR. The majority of subtyped samples (n = 13) were influenza A(H3N2), while only three were B/Victoria. Clinical samples with low Ct values obtained by RT-PCR were used for whole-genome sequencing via next-generation sequencing technology. All collected viruses were distinct from the Southern Hemisphere vaccine strains of the corresponding season but matched with vaccines of the following season. Influenza A(H3N2) strains from Myanmar belonged to clade 2a.3 and shared the highest genetic proximity with Bahraini strains. B/Victoria viruses belonged to clade V1A.3a.2 and were genetically similar to Bangladeshi strains. This study highlights the importance of performing influenza virus surveillance with genetic characterization of the influenza virus in Myanmar, to contribute to global influenza surveillance during the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Diagnostic Virology during the COVID-19 Pandemic - Business as Usual)

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11 pages, 540 KiB

Open AccessCommunication

Low Prevalence of SARS-CoV-2 Antibodies in Canine and Feline Serum Samples Collected during the COVID-19 Pandemic in Hong Kong and Korea

by Yun Young Go, Maura Carrai, Yan Ru Choi, Christopher J. Brackman, Karina W. S. Tam, Pierra Y. T. Law, Fiona Woodhouse, Jane Gray, Ji Hun Kim, Joohyung Park, Chae Won Jeon, Hyomi Jang, Ioannis Magouras, Nicola Decaro, Samuel M. S. Cheng, Malik Peiris, Julia A. Beatty and Vanessa R. Barrs

Viruses 2023, 15(2), 582; https://doi.org/10.3390/v15020582 - 20 Feb 2023

Cited by 5 | Viewed by 2342

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide since its emergence in 2019. Knowing the potential capacity of the virus to adapt to other species, the serological surveillance of SARS-CoV-2 infection in susceptible animals is important. Hong Kong [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide since its emergence in 2019. Knowing the potential capacity of the virus to adapt to other species, the serological surveillance of SARS-CoV-2 infection in susceptible animals is important. Hong Kong and Seoul are two of Asia’s most densely populated urban cities, where companion animals often live in close contact with humans. Sera collected from 1040 cats and 855 dogs during the early phase of the pandemic in Hong Kong and Seoul were tested for SARS-CoV-2 antibodies using an ELISA that detects antibodies against the receptor binding domain of the viral spike protein. Positive sera were also tested for virus neutralizing antibodies using a surrogate virus neutralization (sVNT) and plaque reduction neutralization test (PRNT). Among feline sera, 4.51% and 2.54% of the samples from Korea and Hong Kong, respectively, tested ELISA positive. However, only 1.64% of the samples from Korea and 0.18% from Hong Kong tested positive by sVNT, while only 0.41% of samples from Korea tested positive by PRNT. Among canine samples, 4.94% and 6.46% from Korea and Hong Kong, respectively, tested positive by ELISA, while only 0.29% of sera from Korea were positive on sVNT and no canine sera tested positive by PRNT. These results confirm a low seroprevalence of SARS-CoV-2 exposure in companion animals in Korea and Hong Kong. The discordance between the RBD-ELISA and neutralization tests may indicate possible ELISA cross-reactivity with other coronaviruses, especially in canine sera. Full article

(This article belongs to the Special Issue Viral Infections in Companion Animals: Volume 2)

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21 pages, 3969 KiB

Open AccessArticle

Diverse Marine T4-like Cyanophage Communities Are Primarily Comprised of Low-Abundance Species Including Species with Distinct Seasonal, Persistent, Occasional, or Sporadic Dynamics

by Emily Dart, Jed A. Fuhrman and Nathan A. Ahlgren

Viruses 2023, 15(2), 581; https://doi.org/10.3390/v15020581 - 20 Feb 2023

Cited by 6 | Viewed by 3730

Abstract

Cyanophages exert important top-down controls on their cyanobacteria hosts; however, concurrent analysis of both phage and host populations is needed to better assess phage–host interaction models. We analyzed picocyanobacteria Prochlorococcus and Synechococcus and T4-like cyanophage communities in Pacific Ocean surface waters using five [...] Read more.

Cyanophages exert important top-down controls on their cyanobacteria hosts; however, concurrent analysis of both phage and host populations is needed to better assess phage–host interaction models. We analyzed picocyanobacteria Prochlorococcus and Synechococcus and T4-like cyanophage communities in Pacific Ocean surface waters using five years of monthly viral and cellular fraction metagenomes. Cyanophage communities contained thousands of mostly low-abundance (<2% relative abundance) species with varying temporal dynamics, categorized as seasonally recurring or non-seasonal and occurring persistently, occasionally, or sporadically (detected in ≥85%, 15-85%, or <15% of samples, respectively). Viromes contained mostly seasonal and persistent phages (~40% each), while cellular fraction metagenomes had mostly sporadic species (~50%), reflecting that these sample sets capture different steps of the infection cycle—virions from prior infections or within currently infected cells, respectively. Two groups of seasonal phages correlated to Synechococcus or Prochlorococcus were abundant in spring/summer or fall/winter, respectively. Cyanophages likely have a strong influence on the host community structure, as their communities explained up to 32% of host community variation. These results support how both seasonally recurrent and apparent stochastic processes, likely determined by host availability and different host-range strategies among phages, are critical to phage–host interactions and dynamics, consistent with both the Kill-the-Winner and the Bank models. Full article

(This article belongs to the Section Bacterial Viruses)

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9 pages, 1453 KiB

Open AccessArticle

Search of Novel Small Molecule Inhibitors for the Main Protease of SARS-CoV-2

by Wenfa Zhang and Sheng-Xiang Lin

Viruses 2023, 15(2), 580; https://doi.org/10.3390/v15020580 - 20 Feb 2023

Cited by 5 | Viewed by 2153

Abstract

The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role [...] Read more.

The current outbreak of coronavirus disease 2019 (COVID-19) has prompted the necessity of efficient treatment strategies. The COVID-19 pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Main protease (Mpro), also called 3-chymotrypsin-like protease (3CL protease), plays an essential role in cleaving virus polyproteins for the functional replication complex. Therefore, Mpro is a promising drug target for COVID-19 therapy. Through molecular modelling, docking and a protease activity assay, we found four novel inhibitors targeting Mpro with the half maximal inhibitory concentration (IC50) and their binding affinities shown by the dissociation constants (K_Ds). Our new inhibitors CB-21, CB-25, CP-1 and LC24-20 have IC50s at 14.88 µM (95% Confidence Interval (95% CI): 10.35 µM to 20.48 µM), 22.74 µM (95% CI: 13.01 µM to 38.16 µM), 18.54µM (95% CI: 6.54 µM to 36.30 µM) and 32.87µM (95% CI: 18.37 µM to 54.80 µM)), respectively. The evaluation of interactions suggested that each inhibitor has a hydrogen bond or hydrophobic interactions with important residues, including the most essential catalytic residues: His⁴¹ and Cys¹⁴⁵. All the four inhibitors have a much higher 50% lethal dose (LD50) compared with the well-known Mpro inhibitor GC376, demonstrating its low toxicity. These four inhibitors can be potential drug candidates for further in vitro and in vivo studies against COVID-19. Full article

(This article belongs to the Special Issue Drug-Repositioning Opportunities for Antiviral Therapy: Volume 2)

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18 pages, 2562 KiB

Open AccessArticle

High Prevalence of Alternative Diagnoses in Children and Adolescents with Suspected Long COVID—A Single Center Cohort Study

by Sarah C. Goretzki, Maire Brasseler, Burcin Dogan, Tom Hühne, Daniel Bernard, Anne Schönecker, Mathis Steindor, Andrea Gangfuß, Adela Della Marina, Ursula Felderhoff-Müser, Christian Dohna-Schwake and Nora Bruns

Viruses 2023, 15(2), 579; https://doi.org/10.3390/v15020579 - 20 Feb 2023

Cited by 4 | Viewed by 2445

Abstract

Background: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable [...] Read more.

Background: Long COVID (LC) is a diagnosis that requires exclusion of alternative somatic and mental diseases. The aim of this study was to examine the prevalence of differential diagnoses in suspected pediatric LC patients and assess whether adult LC symptom clusters are applicable to pediatric patients. Materials and Methods: Pediatric presentations at the Pediatric Infectious Diseases Department of the University Hospital Essen (Germany) were assessed retrospectively. The correlation of initial symptoms and final diagnoses (LC versus other diseases or unclarified) was assessed. The sensitivity, specificity, negative and positive predictive values of adult LC symptom clusters were calculated. Results: Of 110 patients, 32 (29%) suffered from LC, 52 (47%) were diagnosed with alternative somatic/mental diseases, and 26 (23%) remained unclarified. Combined neurological and respiratory clusters displayed a sensitivity of 0.97 (95% CI 0.91–1.00) and a negative predictive value of 0.97 (0.92–1.00) for LC. Discussion/Conclusions: The prevalence of alternative somatic and mental diseases in pediatric patients with suspected LC is high. The range of underlying diseases is wide, including chronic and potentially life-threatening conditions. Neurological and respiratory symptom clusters may help to identify patients that are unlikely to be suffering from LC. Full article

(This article belongs to the Special Issue Post-COVID Syndrome)

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17 pages, 1209 KiB

Open AccessReview

Human Coronavirus OC43 as a Low-Risk Model to Study COVID-19

by Mi Il Kim and Choongho Lee

Viruses 2023, 15(2), 578; https://doi.org/10.3390/v15020578 - 20 Feb 2023

Cited by 17 | Viewed by 8533

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has had irreversible and devastating impacts on every aspect of human life. To better prepare for the next similar pandemic, a clear understanding of coronavirus biology is a prerequisite. Nevertheless, the high-risk nature of the causative agent [...] Read more.

The coronavirus disease 2019 (COVID-19) pandemic has had irreversible and devastating impacts on every aspect of human life. To better prepare for the next similar pandemic, a clear understanding of coronavirus biology is a prerequisite. Nevertheless, the high-risk nature of the causative agent of COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), requires the use of a cumbersome biosafety level-3 (BSL-3) confinement facility. To facilitate the development of preventive and therapeutic measures against SARS-CoV-2, one of the endemic strains of low-risk coronaviruses has gained attention as a useful research alternative: human coronavirus OC43 (HCoV-OC43). In this review, its history, classification, and clinical manifestations are first summarized. The characteristics of its viral genomes, genes, and evolution process are then further explained. In addition, the host factors necessary to support the life cycle of HCoV-OC43 and the innate, as well as adaptive, immunological responses to HCoV-OC43 infection are discussed. Finally, the development of in vitro and in vivo systems to study HCoV-OC43 and its application to the discovery of potential antivirals for COVID-19 by using HCoV-OC43 models are also presented. This review should serve as a concise guide for those who wish to use HCoV-OC43 to study coronaviruses in a low-risk research setting. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Coronaviruses)

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21 pages, 563 KiB

Open AccessReview

HIV and COVID-19 Co-Infection: Epidemiology, Clinical Characteristics, and Treatment

by Dimitris Basoulis, Elpida Mastrogianni, Pantazis-Michail Voutsinas and Mina Psichogiou

Viruses 2023, 15(2), 577; https://doi.org/10.3390/v15020577 - 20 Feb 2023

Cited by 11 | Viewed by 3872

Abstract

The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV stigma, are considered a vulnerable population at high risk. In this review, we report what [...] Read more.

The COVID-19 pandemic has been a global medical emergency with a significant socio-economic impact. People with HIV (PWH), due to the underlying immunosuppression and the particularities of HIV stigma, are considered a vulnerable population at high risk. In this review, we report what is currently known in the available literature with regards to the clinical implications of the overlap of the two epidemics. PWH share the same risk factors for severe COVID-19 as the general population (age, comorbidities), but virological and immunological status also plays an important role. Clinical presentation does not differ significantly, but there are some opportunistic infections that can mimic or co-exist with COVID-19. PWH should be prime candidates for preventative COVID-19 treatments when they are available, but in the setting of resistant strains, this might be not easy. When considering small-molecule medications, physicians need to always remember to address potential interactions with ART, and when considering immunosuppressants, they need to be aware of potential risks for opportunistic infections. COVID-19 shares similarities with HIV in how the public perceives patients—with fear of the unknown and prejudice. There are opportunities for HIV treatment hidden in COVID-19 research with the leaps gained in both monoclonal antibody and vaccine development. Full article

(This article belongs to the Special Issue COVID-19 Pharmacotherapy)

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15 pages, 2312 KiB

Open AccessArticle

Introductions of Human-Origin Seasonal H3N2, H1N2 and Pre-2009 H1N1 Influenza Viruses to Swine in Brazil

by Caroline Tochetto, Dennis M. Junqueira, Tavis K. Anderson, Danielle Gava, Vanessa Haach, Mauricio E. Cantão, Amy L. Vincent Baker and Rejane Schaefer

Viruses 2023, 15(2), 576; https://doi.org/10.3390/v15020576 - 19 Feb 2023

Cited by 8 | Viewed by 2870

Abstract

In South America, the evolutionary history of influenza A virus (IAV) in swine has been obscured by historically low levels of surveillance, and this has hampered the assessment of the zoonotic risk of emerging viruses. The extensive genetic diversity of IAV in swine [...] Read more.

In South America, the evolutionary history of influenza A virus (IAV) in swine has been obscured by historically low levels of surveillance, and this has hampered the assessment of the zoonotic risk of emerging viruses. The extensive genetic diversity of IAV in swine observed globally has been attributed mainly to bidirectional transmission between humans and pigs. We conducted surveillance in swine in Brazil during 2011–2020 and characterized 107 H1N1, H1N2, and H3N2 IAVs. Phylogenetic analysis based on HA and NA segments revealed that human seasonal IAVs were introduced at least eight times into swine in Brazil since the mid-late 1980s. Our analyses revealed three genetic clades of H1 within the 1B lineage originated from three distinct spillover events, and an H3 lineage that has diversified into three genetic clades. The N2 segment from human seasonal H1N2 and H3N2 viruses was introduced into swine six times and a single introduction of an N1 segment from the human H1N1 virus was identified. Additional analysis revealed further reassortment with H1N1pdm09 viruses. All these introductions resulted in IAVs that apparently circulate only in Brazilian herds. These results reinforce the significant contributions of human IAVs to the genetic diversity of IAV in swine and reiterate the importance of surveillance of IAV in pigs. Full article

(This article belongs to the Special Issue Advances in Animal Influenza Virus Research)

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18 pages, 1545 KiB

Open AccessArticle

SARS-CoV-2 Vaccine-Induced T-Cell Response after Three Doses in People Living with HIV on Antiretroviral Therapy Compared to Seronegative Controls (CTN 328 COVAXHIV Study)

by Yulia Alexandrova, Alexis Yero, Ralph-Sydney Mboumba Bouassa, Eve Comeau, Suzanne Samarani, Zabrina L. Brumme, Mark Hull, Angela M. Crawley, Marc-André Langlois, Jonathan B. Angel, Curtis L. Cooper, Judy Needham, Terry Lee, Joel Singer, Aslam H. Anis, Cecilia T. Costiniuk and Mohammad-Ali Jenabian

Viruses 2023, 15(2), 575; https://doi.org/10.3390/v15020575 - 19 Feb 2023

Cited by 9 | Viewed by 3147

Abstract

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH [...] Read more.

People living with HIV (PLWH) may be at risk for poor immunogenicity to certain vaccines, including the ability to develop immunological memory. Here, we assessed T-cell immunogenicity following three SARS-CoV-2 vaccine doses in PLWH versus uninfected controls. Blood was collected from 38 PLWH on antiretroviral therapy and 24 age-matched HIV-negative controls, pre-vaccination and after 1st/2nd/3rd dose of SARS-CoV-2 vaccines, without prior SARS-CoV-2 infection. Flow cytometry was used to assess ex vivo T-cell immunophenotypes and intracellular Tumor necrosis factor (TNF)-α/interferon(IFN)-γ/interleukin(IL)-2 following SARS-CoV-2-Spike-peptide stimulation. Comparisons were made using Wilcoxon signed-rank test for paired variables and Mann–Whitney for unpaired. In PLWH, Spike-specific CD4 T-cell frequencies plateaued post-2nd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. PLWH had higher frequencies of TNFα+CD4 T-cells and lower frequencies of IFNγ+CD8 T-cells than seronegative participants post-3rd dose. Regardless of HIV status, an increase in naive, regulatory, and PD1+ T-cell frequencies was observed post-3rd dose. In summary, two doses of SARS-CoV-2 vaccine induced a robust T-cell immune response in PLWH, which was maintained after the 3rd dose, with no significant differences in polyfunctional SARS-CoV-2-specific T-cell proportions between PLWH and uninfected controls post-3rd dose. Full article

(This article belongs to the Special Issue SARS-CoV-2 and Other Vaccines: Immunogenicity Parameters and Protection 2nd Edition)

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15 pages, 12033 KiB

Open AccessReview

Antagonisms of ASFV towards Host Defense Mechanisms: Knowledge Gaps in Viral Immune Evasion and Pathogenesis

by Liangzheng Yu, Zhenbang Zhu, Junhua Deng, Kegong Tian and Xiangdong Li

Viruses 2023, 15(2), 574; https://doi.org/10.3390/v15020574 - 19 Feb 2023

Cited by 7 | Viewed by 3585

Abstract

African swine fever (ASF) causes high morbidity and mortality of both domestic pigs and wild boars and severely impacts the swine industry worldwide. ASF virus (ASFV), the etiologic agent of ASF epidemics, mainly infects myeloid cells in swine mononuclear phagocyte system (MPS), including [...] Read more.

African swine fever (ASF) causes high morbidity and mortality of both domestic pigs and wild boars and severely impacts the swine industry worldwide. ASF virus (ASFV), the etiologic agent of ASF epidemics, mainly infects myeloid cells in swine mononuclear phagocyte system (MPS), including blood-circulating monocytes, tissue-resident macrophages, and dendritic cells (DCs). Since their significant roles in bridging host innate and adaptive immunity, these cells provide ASFV with favorable targets to manipulate and block their antiviral activities, leading to immune escape and immunosuppression. To date, vaccines are still being regarded as the most promising measure to prevent and control ASF outbreaks. However, ASF vaccine development is delayed and limited by existing knowledge gaps in viral immune evasion, pathogenesis, etc. Recent studies have revealed that ASFV can employ diverse strategies to interrupt the host defense mechanisms via abundant self-encoded proteins. Thus, this review mainly focuses on the antagonisms of ASFV-encoded proteins towards IFN-I production, IFN-induced antiviral response, NLRP3 inflammasome activation, and GSDMD-mediated pyroptosis. Additionally, we also make a brief discussion concerning the potential challenges in future development of ASF vaccine. Full article

(This article belongs to the Special Issue Porcine Anti-viral Immunity)

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22 pages, 3784 KiB

Open AccessArticle

The Interplay among Glucocorticoid Therapy, Platelet-Activating Factor and Endocannabinoid Release Influences the Inflammatory Response to COVID-19

by Jonatan C. S. de Carvalho, Pedro V. da Silva-Neto, Diana M. Toro, Carlos A. Fuzo, Viviani Nardini, Vinícius E. Pimentel, Malena M. Pérez, Thais F. C. Fraga-Silva, Camilla N. S. Oliveira, Augusto M. Degiovani, Fátima M. Ostini, Marley R. Feitosa, Rogerio S. Parra, José J. R. da Rocha, Omar Feres, Fernando C. Vilar, Gilberto G. Gaspar, Isabel K. F. M. Santos, Ana P. M. Fernandes, Sandra R. Maruyama, Elisa M. S. Russo, Vânia L. D. Bonato, Cristina R. B. Cardoso, Marcelo Dias-Baruffi, Lúcia H. Faccioli, Carlos A. Sorgi and on behalf of the ImmunoCovid Study Group Show full author list Hide full author list

Viruses 2023, 15(2), 573; https://doi.org/10.3390/v15020573 - 19 Feb 2023

Cited by 4 | Viewed by 3769

Abstract

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid [...] Read more.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course. Full article

(This article belongs to the Special Issue Host Targeted Therapeutics against Virus Infections)

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13 pages, 534 KiB

Open AccessReview

The Role of NS1 Protein in the Diagnosis of Flavivirus Infections

by Ron Fisher, Yaniv Lustig, Ella H. Sklan and Eli Schwartz

Viruses 2023, 15(2), 572; https://doi.org/10.3390/v15020572 - 19 Feb 2023

Cited by 11 | Viewed by 4500

Abstract

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after [...] Read more.

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses’ NS1′s potential role in antigen and antibody diagnosis. Full article

(This article belongs to the Special Issue Boosting Flavivirus Research: A Pandengue Net Initiative)

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13 pages, 1955 KiB

Open AccessArticle

From Capillary Electrophoresis to Deep Sequencing: An Improved HIV-1 Drug Resistance Assessment Solution Using In Vitro Diagnostic (IVD) Assays and Software

by Sofiane Mohamed, Ronan Boulmé and Chalom Sayada

Viruses 2023, 15(2), 571; https://doi.org/10.3390/v15020571 - 19 Feb 2023

Cited by 4 | Viewed by 2188

Abstract

Background: Drug-resistance mutations were mostly detected using capillary electrophoresis sequencing, which does not detect minor variants with a frequency below 20%. Next-Generation Sequencing (NGS) can now detect additional mutations which can be useful for HIV-1 drug resistance interpretation. The objective of this study [...] Read more.

Background: Drug-resistance mutations were mostly detected using capillary electrophoresis sequencing, which does not detect minor variants with a frequency below 20%. Next-Generation Sequencing (NGS) can now detect additional mutations which can be useful for HIV-1 drug resistance interpretation. The objective of this study was to evaluate the performances of CE-IVD assays for HIV-1 drug-resistance assessment both for target-specific and whole-genome sequencing, using standardized end-to-end solution platforms. Methods: A total of 301 clinical samples were prepared, extracted, and amplified for the three HIV-1 genomic targets, Protease (PR), Reverse Transcriptase (RT), and Integrase (INT), using the CE-IVD DeepChek^® Assays; and then 19 clinical samples, using the CE-IVD DeepChek^® HIV Whole Genome Assay, were sequenced on the NGS iSeq100 and MiSeq (Illumina, San Diego, CA, USA). Sequences were compared to those obtained by capillary electrophoresis. Quality control for Molecular Diagnostics (QCMD) samples was added to validate the clinical accuracy of these in vitro diagnostics (IVDs). Nineteen clinical samples were then tested with the same sample collection, handling, and measurement procedure for evaluating the use of NGS for whole-genome HIV-1. Sequencing analyzer outputs were submitted to a downstream CE-IVD standalone software tailored for HIV-1 analysis and interpretation. Results: The limits of range detection were 1000 to 10⁶ cp/mL for the HIV-1 target-specific sequencing. The median coverage per sample for the three amplicons (PR/RT and INT) was 13,237 reads. High analytical reproducibility and repeatability were evidenced by a positive percent agreement of 100%. Duplicated samples in two distinct NGS runs were 100% homologous. NGS detected all the mutations found by capillary electrophoresis and identified additional resistance variants. A perfect accuracy score with the QCMD panel detection of drug-resistance mutations was obtained. Conclusions: This study is the first evaluation of the DeepChek^® Assays for targets specific (PR/RT and INT) and whole genome. A cutoff of 3% allowed for a better characterization of the viral population by identifying additional resistance mutations and improving the HIV-1 drug-resistance interpretation. The use of whole-genome sequencing is an additional and complementary tool to detect mutations in newly infected untreated patients and heavily experienced patients, both with higher HIV-1 viral-load profiles, to offer new insight and treatment strategies, especially using the new HIV-1 capsid/maturation inhibitors and to assess the potential clinical impact of mutations in the HIV-1 genome outside of the usual HIV-1 targets (RT/PR and INT). Full article

(This article belongs to the Special Issue HIV Epidemiology and Drug Resistance)

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18 pages, 4147 KiB

Open AccessArticle

Fragment-Based Approaches Identified Tecovirimat-Competitive Novel Drug Candidate for Targeting the F13 Protein of the Monkeypox Virus

by Yasir Ali, Hina Imtiaz, Muhammad Mutaal Tahir, Fouzia Gul, Umair Ali Khan Saddozai, Ashfaq ur Rehman, Zhi-Guang Ren, Saadullah Khattak and Xin-Ying Ji

Viruses 2023, 15(2), 570; https://doi.org/10.3390/v15020570 - 19 Feb 2023

Cited by 13 | Viewed by 3013

Abstract

Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be [...] Read more.

Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand–enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation. Full article

(This article belongs to the Special Issue Virus Bioinformatics 2023)

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16 pages, 4433 KiB

Open AccessArticle

Genomic Epidemiology and Transmission Dynamics of Global Coxsackievirus B4

by Jinbo Xiao, Jianxing Wang, Huanhuan Lu, Yang Song, Dapeng Sun, Zhenzhi Han, Jichen Li, Qian Yang, Dongmei Yan, Shuangli Zhu, Yaowen Pei, Xianjun Wang, Wenbo Xu and Yong Zhang

Viruses 2023, 15(2), 569; https://doi.org/10.3390/v15020569 - 19 Feb 2023

Cited by 4 | Viewed by 2032

Abstract

The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity [...] Read more.

The aim of this study was to determine the global genetic diversity and transmission dynamics of coxsackievirus B4 (CVB4) and to propose future directions for disease surveillance. Next-generation sequencing was performed to obtain the complete genome sequence of CVB4, and the genetic diversity and transmission dynamics of CVB4 worldwide were analyzed using bioinformatics methods such as phylogenetic analysis, evolutionary dynamics, and phylogeographic analysis. Forty complete genomes of CVB4 were identified from asymptomatic infected individuals and hand, foot, and mouth disease (HFMD) patients. Frequent recombination between CVB4 and EV-B multiple serotypes in the 3D^pol region was found and formed 12 recombinant patterns (A-L). Among these, the CVB4 isolated from asymptomatic infected persons and HFMD patients belonged to lineages H and I, respectively. Transmission dynamics analysis based on the VP1 region revealed that CVB4 epidemics in countries outside China were dominated by the D genotype, whereas the E genotype was dominant in China, and both genotypes evolved at a rate of > 6.50 × 10⁻³ substitutions/site/year. CVB4 spreads through the population unseen, with the risk of disease outbreaks persisting as susceptible individuals accumulate. Our findings add to publicly available CVB4 genomic sequence data and deepen our understanding of CVB4 molecular epidemiology. Full article

(This article belongs to the Special Issue Coxsackieviruses and Associated Diseases)

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46 pages, 27660 KiB

Open AccessReview

Targeting Human Proteins for Antiviral Drug Discovery and Repurposing Efforts: A Focus on Protein Kinases

by Rima Hajjo, Dima A. Sabbah, Osama H. Abusara, Reham Kharmah and Sanaa Bardaweel

Viruses 2023, 15(2), 568; https://doi.org/10.3390/v15020568 - 19 Feb 2023

Cited by 3 | Viewed by 3712

Abstract

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, and existing antivirals suffer from major limitations regarding drug resistance and a limited spectrum of activity. In fact, most approved antivirals are directly [...] Read more.

Despite the great technological and medical advances in fighting viral diseases, new therapies for most of them are still lacking, and existing antivirals suffer from major limitations regarding drug resistance and a limited spectrum of activity. In fact, most approved antivirals are directly acting antiviral (DAA) drugs, which interfere with viral proteins and confer great selectivity towards their viral targets but suffer from resistance and limited spectrum. Nowadays, host-targeted antivirals (HTAs) are on the rise, in the drug discovery and development pipelines, in academia and in the pharmaceutical industry. These drugs target host proteins involved in the virus life cycle and are considered promising alternatives to DAAs due to their broader spectrum and lower potential for resistance. Herein, we discuss an important class of HTAs that modulate signal transduction pathways by targeting host kinases. Kinases are considered key enzymes that control virus-host interactions. We also provide a synopsis of the antiviral drug discovery and development pipeline detailing antiviral kinase targets, drug types, therapeutic classes for repurposed drugs, and top developing organizations. Furthermore, we detail the drug design and repurposing considerations, as well as the limitations and challenges, for kinase-targeted antivirals, including the choice of the binding sites, physicochemical properties, and drug combinations. Full article

(This article belongs to the Special Issue Drug-Repositioning Opportunities for Antiviral Therapy: Volume 2)

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14 pages, 1797 KiB

Open AccessArticle

Definition of a New HLA B*52-Restricted Rev CTL Epitope Targeted by an HIV-1-Infected Controller

by Boutaina El Kenz, Katja G. Schmidt, Victoria K. Ogungbemi-Alt, Silke Bergmann, Philipp Steininger, Klaus Korn, Bernd Spriewald, Ellen G. Harrer, Krystelle Nganou-Makamdop and Thomas Harrer

Viruses 2023, 15(2), 567; https://doi.org/10.3390/v15020567 - 18 Feb 2023

Viewed by 1727

Abstract

The analysis of T-cell responses in HIV-1-infected controllers may contribute to a better understanding of the protective components of the immune system. Here, we analyzed the HIV-1-specific T-cell response in a 59-year-old HIV-1-infected controller, infected for at least seven years, who presented with [...] Read more.

The analysis of T-cell responses in HIV-1-infected controllers may contribute to a better understanding of the protective components of the immune system. Here, we analyzed the HIV-1-specific T-cell response in a 59-year-old HIV-1-infected controller, infected for at least seven years, who presented with low viral loads ranging from <20 copies/mL to 200 copies/mL and normal CD4 counts of >800 cells/µL. In γ-IFN-ELISpot assays using freshly isolated PBMCs, he displayed a very strong polyclonal T-cell response to eight epitopes in Gag, Nef and Rev; with the dominant responses directed against the HLA-B*57-epitope AISPRTLNAW and against a so-far-unknown epitope within Rev. Further analyses using peptide-stimulated T-cell lines in γ-IFN-ELISpot assays delineated the peptide RQRQIRSI (Rev-RI8) as a newly defined HLA-B*52-restricted epitope located within a functionally important region of Rev. Peptide-stimulation assays in 15 HLA-B*52-positive HIV-1-infected subjects, including the controller, demonstrated recognition of the Rev-RI8 epitope in 6/15 subjects. CD4 counts before the start of antiviral therapy were significantly higher in subjects with recognition of the Rev-RI8 epitope. Targeting of the Rev-RI8 epitope in Rev by CTL could contribute to the positive association of HLA-B*52 with a more favorable course of HIV-1-infection. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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11 pages, 1763 KiB

Open AccessArticle

Evaluation of the Function of ASFV Gene E66L in the Process of Virus Replication and Virulence in Swine

by Elizabeth Ramirez-Medina, Elizabeth A. Vuono, Ayushi Rai, Nallely Espinoza, Alyssa Valladares, Edward Spinard, Lauro Velazquez-Salinas, Douglas P. Gladue and Manuel V. Borca

Viruses 2023, 15(2), 566; https://doi.org/10.3390/v15020566 - 18 Feb 2023

Cited by 1 | Viewed by 2211

Abstract

African swine fever virus (ASFV) is the etiological agent of an economically important disease of swine currently affecting large areas of Africa, Eurasia and the Caribbean. ASFV has a complex structure harboring a large dsDNA genome which encodes for more than 160 proteins. [...] Read more.

African swine fever virus (ASFV) is the etiological agent of an economically important disease of swine currently affecting large areas of Africa, Eurasia and the Caribbean. ASFV has a complex structure harboring a large dsDNA genome which encodes for more than 160 proteins. One of the proteins, E66L, has recently been involved in arresting gene transcription in the infected host cell. Here, we investigate the role of E66L in the processes of virus replication in swine macrophages and disease production in domestic swine. A recombinant ASFV was developed (ASFV-G-∆E66L), from the virulent parental Georgia 2010 isolate (ASFV-G), harboring the deletion of the E66L gene as a tool to assess the role of the gene. ASFV-G-∆E66L showed that the E66L gene is non-essential for ASFV replication in primary swine macrophages when compared with the parental highly virulent field isolate ASFV-G. Additionally, domestic pigs infected with ASFV-G-∆E66L developed a clinical disease undistinguishable from that produced by ASFV-G. Therefore, E66L is not involved in virus replication or virulence in domestic pigs. Full article

(This article belongs to the Special Issue African Swine Fever Virus 3.0)

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8 pages, 971 KiB

Open AccessCase Report

Metagenomic Approach Reveals the Second Subtype of PRRSV-1 in a Pathogen Spectrum during a Clinical Outbreak with High Mortality in Western Siberia, Russia

by Nikita Krasnikov, Anton Yuzhakov, Taras Aliper and Alexey Gulyukin

Viruses 2023, 15(2), 565; https://doi.org/10.3390/v15020565 - 18 Feb 2023

Cited by 2 | Viewed by 2474

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) has a significant economic impact on pig farming worldwide by causing reproductive problems and affecting the respiratory systems of swine. In Eastern Europe, PRRSV-1 strains are characterized by high genetic variability, and pathogenicity differs among all [...] Read more.

Porcine reproductive and respiratory syndrome virus (PRRSV) has a significant economic impact on pig farming worldwide by causing reproductive problems and affecting the respiratory systems of swine. In Eastern Europe, PRRSV-1 strains are characterized by high genetic variability, and pathogenicity differs among all known subtypes. This case study describes the detection of a wide pathogen spectrum, including the second subtype PRRSV-1, with a high mortality rate among nursery piglets (23.8%). This study was conducted at a farrow-to-finish farm in the Western Siberia region of Russia. Clinical symptoms included apathy, sneezing, and an elevation in body temperature, and during the autopsy, degenerative lesions in different tissues were observed. Moreover, 1.5 percent of the affected animals displayed clinical signs of the central nervous system and were characterized by polyserositis. Nasal swabs from diseased piglets and various tissue swabs from deceased animals were studied. For diagnostics, the nanopore sequencing method was applied. All the samples tested positive for PRRSV, and a more detailed analysis defined it as a second subtype of PRRSV-1. The results, along with the clinical picture, showed a complex disease etiology with the dominant role of PRRSV-1 and were informative about the high pathogenicity of the subtype in question under field conditions. Full article

(This article belongs to the Section Animal Viruses)

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16 pages, 2309 KiB

Open AccessArticle

An Update on Eukaryotic Viruses Revived from Ancient Permafrost

by Jean-Marie Alempic, Audrey Lartigue, Artemiy E. Goncharov, Guido Grosse, Jens Strauss, Alexey N. Tikhonov, Alexander N. Fedorov, Olivier Poirot, Matthieu Legendre, Sébastien Santini, Chantal Abergel and Jean-Michel Claverie

Viruses 2023, 15(2), 564; https://doi.org/10.3390/v15020564 - 18 Feb 2023

Cited by 21 | Viewed by 47555

Abstract

One quarter of the Northern hemisphere is underlain by permanently frozen ground, referred to as permafrost. Due to climate warming, irreversibly thawing permafrost is releasing organic matter frozen for up to a million years, most of which decomposes into carbon dioxide and methane, [...] Read more.

One quarter of the Northern hemisphere is underlain by permanently frozen ground, referred to as permafrost. Due to climate warming, irreversibly thawing permafrost is releasing organic matter frozen for up to a million years, most of which decomposes into carbon dioxide and methane, further enhancing the greenhouse effect. Part of this organic matter also consists of revived cellular microbes (prokaryotes, unicellular eukaryotes) as well as viruses that have remained dormant since prehistorical times. While the literature abounds on descriptions of the rich and diverse prokaryotic microbiomes found in permafrost, no additional report about “live” viruses have been published since the two original studies describing pithovirus (in 2014) and mollivirus (in 2015). This wrongly suggests that such occurrences are rare and that “zombie viruses” are not a public health threat. To restore an appreciation closer to reality, we report the preliminary characterizations of 13 new viruses isolated from seven different ancient Siberian permafrost samples, one from the Lena river and one from Kamchatka cryosol. As expected from the host specificity imposed by our protocol, these viruses belong to five different clades infecting Acanthamoeba spp. but not previously revived from permafrost: Pandoravirus, Cedratvirus, Megavirus, and Pacmanvirus, in addition to a new Pithovirus strain. Full article

(This article belongs to the Special Issue Research Progresses of Giant Viruses: A Themed Issue Dedicated to Professor Jean-Michel Claverie)

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22 pages, 2441 KiB

Open AccessArticle

Cross-Hemispheric Genetic Diversity and Spatial Genetic Structure of Callinectes sapidus Reovirus 1 (CsRV1)

by Mingli Zhao, Louis V. Plough, Donald C. Behringer, Jamie Bojko, Andrew S. Kough, Nathaniel W. Alper, Lan Xu and Eric J. Schott

Viruses 2023, 15(2), 563; https://doi.org/10.3390/v15020563 - 18 Feb 2023

Cited by 2 | Viewed by 2900

Abstract

The movement of viruses in aquatic systems is rarely studied over large geographic scales. Oceanic currents, host migration, latitude-based variation in climate, and resulting changes in host life history are all potential drivers of virus connectivity, adaptation, and genetic structure. To expand our [...] Read more.

The movement of viruses in aquatic systems is rarely studied over large geographic scales. Oceanic currents, host migration, latitude-based variation in climate, and resulting changes in host life history are all potential drivers of virus connectivity, adaptation, and genetic structure. To expand our understanding of the genetic diversity of Callinectes sapidus reovirus 1 (CsRV1) across a broad spatial and host life history range of its blue crab host (Callinectes sapidus), we obtained 22 complete and 96 partial genomic sequences for CsRV1 strains from the US Atlantic coast, Gulf of Mexico, Caribbean Sea, and the Atlantic coast of South America. Phylogenetic analyses of CsRV1 genomes revealed that virus genotypes were divided into four major genogroups consistent with their host geographic origins. However, some CsRV1 sequences from the US mid-Atlantic shared high genetic similarity with the Gulf of Mexico genotypes, suggesting potential human-mediated movement of CsRV1 between the US mid-Atlantic and Gulf coasts. This study advances our understanding of how climate, coastal geography, host life history, and human activity drive patterns of genetic structure and diversity of viruses in marine animals and contributes to the capacity to infer broadscale host population connectivity in marine ecosystems from virus population genetic data. Full article

(This article belongs to the Section Animal Viruses)

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22 pages, 760 KiB

Open AccessReview

The Host Non-Coding RNA Response to Alphavirus Infection

by Mahgol Behnia and Steven B. Bradfute

Viruses 2023, 15(2), 562; https://doi.org/10.3390/v15020562 - 18 Feb 2023

Cited by 2 | Viewed by 2766

Abstract

Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but [...] Read more.

Alphaviruses are important human and animal pathogens that can cause a range of debilitating symptoms and are found worldwide. These include arthralgic diseases caused by Old-World viruses and encephalitis induced by infection with New-World alphaviruses. Non-coding RNAs do not encode for proteins, but can modulate cellular response pathways in a myriad of ways. There are several classes of non-coding RNAs, some more well-studied than others. Much research has focused on the mRNA response to infection against alphaviruses, but analysis of non-coding RNA responses has been more limited until recently. This review covers what is known regarding host cell non-coding RNA responses in alphavirus infections and highlights gaps in the knowledge that future research should address. Full article

(This article belongs to the Special Issue RNA Biology of Viral Infection)

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25 pages, 1839 KiB

Open AccessReview

Hemorrhagic Fever with Renal Syndrome in Asia: History, Pathogenesis, Diagnosis, Treatment, and Prevention

by Ayushi Sehgal, Sanya Mehta, Kritika Sahay, Ekaterina Martynova, Albert Rizvanov, Manoj Baranwal, Sara Chandy, Svetlana Khaiboullina, Emmanuel Kabwe and Yuriy Davidyuk

Viruses 2023, 15(2), 561; https://doi.org/10.3390/v15020561 - 18 Feb 2023

Cited by 23 | Viewed by 4795

Abstract

Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute [...] Read more.

Hemorrhagic Fever with Renal Syndrome (HFRS) is the most frequently diagnosed zoonosis in Asia. This zoonotic infection is the result of exposure to the virus-contaminated aerosols. Orthohantavirus infection may cause Hemorrhagic Fever with Renal Syndrome (HRFS), a disease that is characterized by acute kidney injury and increased vascular permeability. Several species of orthohantaviruses were identified as causing infection, where Hantaan, Puumala, and Seoul viruses are most common. Orthohantaviruses are endemic to several Asian countries, such as China, South Korea, and Japan. Along with those countries, HFRS tops the list of zoonotic infections in the Far Eastern Federal District of Russia. Recently, orthohantavirus circulation was demonstrated in small mammals in Thailand and India, where orthohantavirus was not believed to be endemic. In this review, we summarized the current data on orthohantaviruses in Asia. We gave the synopsis of the history and diversity of orthohantaviruses in Asia. We also described the clinical presentation and current understanding of the pathogenesis of orthohantavirus infection. Additionally, conventional and novel approaches for preventing and treating orthohantavirus infection are discussed. Full article

(This article belongs to the Special Issue Hantavirus 2022)

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17 pages, 4841 KiB

Open AccessArticle

Evaluating Data Sharing of SARS-CoV-2 Genomes for Molecular Epidemiology across the COVID-19 Pandemic

by Teresa Rito, Pedro Fernandes, Raquel Duarte and Pedro Soares

Viruses 2023, 15(2), 560; https://doi.org/10.3390/v15020560 - 17 Feb 2023

Cited by 3 | Viewed by 1937

Abstract

Following the emergence of COVID-19 in December 2019, caused by the coronavirus SARS-CoV-2, the disease spread dramatically worldwide. The use of genomics to trace the dissemination of the virus and the identification of novel variants was essential in defining measures for containing the [...] Read more.

Following the emergence of COVID-19 in December 2019, caused by the coronavirus SARS-CoV-2, the disease spread dramatically worldwide. The use of genomics to trace the dissemination of the virus and the identification of novel variants was essential in defining measures for containing the disease. We aim to evaluate the global effort to genomically characterize the circulating lineages of SARS-CoV-2, considering the data deposited in GISAID, the major platform for data sharing in a massive worldwide collaborative undertaking. We contextualize data for nearly three years (January 2020–October 2022) for the major contributing countries, percentage of characterized isolates and time for data processing in the context of the global pandemic. Within this collaborative effort, we also evaluated the early detection of seven major SARS-CoV-2 lineages, G, GR, GH, GK, GV, GRY and GRA. While Europe and the USA, following an initial period, showed positive results across time in terms of cases sequenced and time for data deposition, this effort is heterogeneous worldwide. Given the current immunization the major threat is the appearance of variants that evade the acquired immunity. In that scenario, the monitoring of those hypothetical variants will still play an essential role. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2)

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20 pages, 345 KiB

Open AccessReview

Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection

by Tsai-Hsuan Yang, Chi Chan, Po-Jiun Yang, Yu-Han Huang and Mei-Hsuan Lee

Viruses 2023, 15(2), 559; https://doi.org/10.3390/v15020559 - 17 Feb 2023

Cited by 10 | Viewed by 3047

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk [...] Read more.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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Viruses, Volume 15, Issue 2 (February 2023) – 329 articles

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