Viruses

18 pages, 2594 KiB

Open AccessArticle

Characteristics of Subtype and Molecular Transmission Networks among Newly Diagnosed HIV-1 Infections in Patients Residing in Taiyuan City, Shanxi Province, China, from 2021 to 2023

by Ruihong Gao, Wentong Li, Jihong Xu, Jiane Guo, Rui Wang, Shuting Zhang, Xiaonan Zheng and Jitao Wang

Viruses 2024, 16(7), 1174; https://doi.org/10.3390/v16071174 - 22 Jul 2024

Viewed by 672

Abstract

The HIV-1 pandemic, spanning four decades, presents a significant challenge to global public health. This study aimed to understand the molecular transmission characteristics of newly reported HIV infections in Taiyuan, Shanxi Province, China, to analyze the characteristics of subtypes and the risk factors [...] Read more.

The HIV-1 pandemic, spanning four decades, presents a significant challenge to global public health. This study aimed to understand the molecular transmission characteristics of newly reported HIV infections in Taiyuan, Shanxi Province, China, to analyze the characteristics of subtypes and the risk factors of the transmission network, providing a scientific basis for precise prevention and intervention measures. A total of 720 samples were collected from newly diagnosed HIV-1 patients residing in Taiyuan between 2021 and 2023. Sequencing of partial genes of the HIV-1 pol gene resulted in multiple sequence acquisitions and was conducted to analyze their subtypes and molecular transmission networks. Out of the samples, 584 pol sequences were obtained, revealing 17 HIV-1 subtypes, with CRF07_BC (48.29%), CRF01_AE (31.34%), and CRF79_0107 (7.19%) being the dominant subtypes. Using a genetic distance threshold of 1.5%, 49 molecular transmission clusters were generated from the 313 pol gene sequences. Univariate analysis showed significant differences in the HIV transmission molecular network in terms of HIV subtype and household registration (p < 0.05). Multivariate logistic regression analysis showed that CRF79_0107 subtype and its migrants were associated with higher proportions of sequences in the HIV transmission network. These findings provide a scientific foundation for the development of localized HIV-specific intervention strategies. Full article

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

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23 pages, 6811 KiB

Open AccessArticle

The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection

by Alexandra Melton, Lori A. Rowe, Toni Penney, Clara Krzykwa, Kelly Goff, Sarah E. Scheuermann, Hunter J. Melton, Kelsey Williams, Nadia Golden, Kristyn Moore Green, Brandon Smith, Kasi Russell-Lodrigue, Jason P. Dufour, Lara A. Doyle-Meyers, Faith Schiro, Pyone P. Aye, Jeffery D. Lifson, Brandon J. Beddingfield, Robert V. Blair, Rudolf P. Bohm, Jay K. Kolls, Jay Rappaport, James A. Hoxie and Nicholas J. Maness Show full author list Hide full author list

Viruses 2024, 16(7), 1173; https://doi.org/10.3390/v16071173 - 21 Jul 2024

Viewed by 1765

Abstract

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to [...] Read more.

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2. Full article

(This article belongs to the Special Issue Simian Immunodeficiency Virus Models of HIV/AIDS in Nonhuman Primates 2024)

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19 pages, 8930 KiB

Open AccessArticle

Aedes Mosquito Virome in Southwestern Cameroon: Lack of Core Virome, But a Very Rich and Diverse Virome in Ae. africanus Compared to Other Aedes Species

by Karelle Celes Mbigha Donfack, Lander De Coninck, Stephen Mbigha Ghogomu and Jelle Matthijnssens

Viruses 2024, 16(7), 1172; https://doi.org/10.3390/v16071172 - 21 Jul 2024

Viewed by 918

Abstract

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four [...] Read more.

In Cameroon, Aedes mosquitoes transmit various arboviruses, posing significant health risks. We aimed to characterize the Aedes virome in southwestern Cameroon and identify potential core viruses which might be associated with vector competence. A total of 398 Aedes mosquitoes were collected from four locations (Bafoussam, Buea, Edea, and Yaounde). Aedes albopictus dominated all sites except for Bafoussam, where Aedes africanus prevailed. Metagenomic analyses of the mosquitoes grouped per species into 54 pools revealed notable differences in the eukaryotic viromes between Ae. africanus and Ae. albopictus, with the former exhibiting greater richness and diversity. Thirty-seven eukaryotic virus species from 16 families were identified, including six novel viruses with near complete genome sequences. Seven viruses were further quantified in individual mosquitoes via qRT-PCR. Although none of them could be identified as core viruses, Guangzhou sobemo-like virus and Bafoussam mosquito solemovirus, were highly prevalent regionally in Ae. albopictus and Ae. africanus, respectively. This study highlights the diverse eukaryotic virome of Aedes species in southwestern Cameroon. Despite their shared genus, Aedes species exhibit limited viral sharing, with varying viral abundance and prevalence across locations. Ae. africanus, an understudied vector, harbors a rich and diverse virome, suggesting potential implications for arbovirus vector competence. Full article

(This article belongs to the Special Issue Virus Bioinformatics 2024)

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17 pages, 1001 KiB

Open AccessReview

The Interactions of the Complement System with Human Cytomegalovirus

by Eduardo Lujan, Isadora Zhang, Andrea Canto Garon and Fenyong Liu

Viruses 2024, 16(7), 1171; https://doi.org/10.3390/v16071171 - 20 Jul 2024

Viewed by 933

Abstract

The complement system is an evolutionarily ancient component of innate immunity that serves as an important first line of defense against pathogens, including viruses. In response to infection, the complement system can be activated by three distinct yet converging pathways (classical, lectin, and [...] Read more.

The complement system is an evolutionarily ancient component of innate immunity that serves as an important first line of defense against pathogens, including viruses. In response to infection, the complement system can be activated by three distinct yet converging pathways (classical, lectin, and alternative) capable of engaging multiple antiviral host responses to confront acute, chronic, and recurrent viral infections. Complement can exert profound antiviral effects via multiple mechanisms including the induction of inflammation and chemotaxis to sites of infection, neutralization/opsonization of viruses and virally infected cells, and it can even shape adaptive immune responses. With millions of years of co-evolution and the ability to establish life-long infections, herpesviruses have evolved unique mechanisms to counter complement-mediated antiviral defenses, thus enabling their survival and replication within humans. This review aims to comprehensively summarize how human herpesviruses engage with the complement system and highlight our understanding of the role of complement in human cytomegalovirus (HCMV) infection, immunity, and viral replication. Herein we describe the novel and unorthodox roles of complement proteins beyond their roles in innate immunity and discuss gaps in knowledge and future directions of complement and HCMV research. Full article

(This article belongs to the Special Issue 65-Year Anniversary of the Discovery of Cytomegalovirus)

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19 pages, 1192 KiB

Open AccessArticle

African Swine Fever Virus Protein–Protein Interaction Prediction

by Jacob A. Fenster, Paul A. Azzinaro, Mark Dinhobl, Manuel V. Borca, Edward Spinard and Douglas P. Gladue

Viruses 2024, 16(7), 1170; https://doi.org/10.3390/v16071170 - 20 Jul 2024

Cited by 1 | Viewed by 1095

Abstract

The African swine fever virus (ASFV) is an often deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing effective vaccines for this virus remains a challenge due [...] Read more.

The African swine fever virus (ASFV) is an often deadly disease in swine and poses a threat to swine livestock and swine producers. With its complex genome containing more than 150 coding regions, developing effective vaccines for this virus remains a challenge due to a lack of basic knowledge about viral protein function and protein–protein interactions between viral proteins and between viral and host proteins. In this work, we identified ASFV-ASFV protein–protein interactions (PPIs) using artificial intelligence-powered protein structure prediction tools. We benchmarked our PPI identification workflow on the Vaccinia virus, a widely studied nucleocytoplasmic large DNA virus, and found that it could identify gold-standard PPIs that have been validated in vitro in a genome-wide computational screening. We applied this workflow to more than 18,000 pairwise combinations of ASFV proteins and were able to identify seventeen novel PPIs, many of which have corroborating experimental or bioinformatic evidence for their protein–protein interactions, further validating their relevance. Two protein–protein interactions, I267L and I8L, I267L__I8L, and B175L and DP79L, B175L__DP79L, are novel PPIs involving viral proteins known to modulate host immune response. Full article

(This article belongs to the Section Animal Viruses)

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13 pages, 259 KiB

Open AccessArticle

Prevalence of HTLV-1 and Hepatitis B Surface Antigen (HBsAg) Positivity among MSM Attending a Large HIV Treatment Centre in Trinidad

by Robert Jeffrey Edwards, Selena Todd, Jonathan Edwards, Noreen Jack and Gregory Boyce

Viruses 2024, 16(7), 1169; https://doi.org/10.3390/v16071169 - 20 Jul 2024

Viewed by 823

Abstract

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a [...] Read more.

HIV-1, Hepatitis B and HTLV-1 have similar risk factors and shared routes of transmission and MSM are disproportionately affected by HIV. The aim of the study was to determine the prevalence of HTLV-1 and HBsAg positivity at initial enrolment among MSM attending a large HIV Clinic in Trinidad. Chart reviews were conducted between 2 and 15 January 2024, among self-identified MSM and a comparative group of randomly selected self-identified heterosexual males where sociodemographic, clinical and laboratory data were collected and analysed using SPSS Version 25. During the period April 2002–31 October 2023, in total there were 10,424 patients registered at the clinic, of whom 1255 (12.0%) were self-identified MSM, with an age range of 19–85 years and a median age of 40 years. There were 1822 randomly selected heterosexual males, with an age range of 18–94 years old and a median age of 52 years. Among the MSM, there were 21 (1.67%) patients who were HIV-1/HTLV-1-coinfected, 64 (5.10%) who were HIV-1/HBsAg-coinfected and two (0.16%) who were coinfected with all three viruses (HIV-1/HTLV-1/HBsAg) as compared to 47 ((2.58%) HIV-1/HTLV-1-coinfected (p = 0.12), 69 (3.79%) HIV-1/HBsAg-coinfected (p = 0.10) and three (0.16%) patients coinfected with all three viruses among the heterosexual males. There were no patients with HTLV-1-related diseases among the HIV-1/HTLV-1-coinfected patients and there were no deaths from chronic liver disease in patients coinfected with HIV-1/HBsAg. Despite the availability of an efficacious vaccine, there is a prevalence of hepatitis B of 5.1% among MSM attending the HIV Clinic in Trinidad; therefore, programmes to increase health literacy, screening and immunization are urgently needed. Full article

(This article belongs to the Special Issue HIV and HTLV Infections and Coinfections)

14 pages, 2789 KiB

Open AccessArticle

Specific and Sensitive Visual Proviral DNA Detection of Major Pathogenic Avian Leukosis Virus Subgroups Using CRISPR-Associated Nuclease Cas13a

by Qingqing Xu, Yaoyao Zhang, Yashar Sadigh, Na Tang, Jiaqian Chai, Ziqiang Cheng, Yulong Gao, Aijian Qin, Zhiqiang Shen, Yongxiu Yao and Venugopal Nair

Viruses 2024, 16(7), 1168; https://doi.org/10.3390/v16071168 - 20 Jul 2024

Viewed by 908

Abstract

Avian leukosis viruses (ALVs) include a group of avian retroviruses primarily associated with neoplastic diseases in poultry, commonly referred to as avian leukosis. Belonging to different subgroups based on their envelope properties, ALV subgroups A, B, and J (ALV-A, ALV-B, and ALV-J) are [...] Read more.

Avian leukosis viruses (ALVs) include a group of avian retroviruses primarily associated with neoplastic diseases in poultry, commonly referred to as avian leukosis. Belonging to different subgroups based on their envelope properties, ALV subgroups A, B, and J (ALV-A, ALV-B, and ALV-J) are the most widespread in poultry populations. Early identification and removal of virus-shedding birds from infected flocks are essential for the ALVs’ eradication. Therefore, the development of rapid, accurate, simple-to-use, and cost effective on-site diagnostic methods for the detection of ALV subgroups is very important. Cas13a, an RNA-guided RNA endonuclease that cleaves target single-stranded RNA, also exhibits non-specific endonuclease activity on any bystander RNA in close proximity. The distinct trans-cleavage activity of Cas13 has been exploited in the molecular diagnosis of multiple pathogens including several viruses. Here, we describe the development and application of a highly sensitive Cas13a-based molecular test for the specific detection of proviral DNA of ALV-A, B, and J subgroups. Prokaryotically expressed LwaCas13a, purified through ion exchange and size-exclusion chromatography, was combined with recombinase polymerase amplification (RPA) and T7 transcription to establish the SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) molecular detection system for the detection of proviral DNA of ALV-A/B/J subgroups. This novel method that needs less sample input with a short turnaround time is based on isothermal detection at 37 °C with a color-based lateral flow readout. The detection limit of the assay for ALV-A/B/J subgroups was 50 copies with no cross reactivity with ALV-C/D/E subgroups and other avian oncogenic viruses such as reticuloendotheliosis virus (REV) and Marek’s disease virus (MDV). The development and evaluation of a highly sensitive and specific visual method of detection of ALV-A/B/J nucleic acids using CRISPR-Cas13a described here will help in ALV detection in eradication programs. Full article

(This article belongs to the Special Issue Recent Advances of Avian Viruses Research)

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12 pages, 1079 KiB

Open AccessCommunication

NTB-A and 2B4 Natural Killer Cell Receptors Modulate the Capacity of a Cocktail of Non-Neutralizing Antibodies and a Small CD4-Mimetic to Eliminate HIV-1-Infected Cells by Antibody-Dependent Cellular Cytotoxicity

by Lorie Marchitto, Alexandra Tauzin, Mehdi Benlarbi, Guillaume Beaudoin-Bussières, Katrina Dionne, Étienne Bélanger, Debashree Chatterjee, Catherine Bourassa, Halima Medjahed, Derek Yang, Ta-Jung Chiu, Hung-Ching Chen, Amos B. Smith III, Jonathan Richard and Andrés Finzi

Viruses 2024, 16(7), 1167; https://doi.org/10.3390/v16071167 - 20 Jul 2024

Viewed by 882

Abstract

Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion [...] Read more.

Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a “closed” conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC. Full article

(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)

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16 pages, 7912 KiB

Open AccessArticle

HIV-1 Intasomes Assembled with Excess Integrase C-Terminal Domain Protein Facilitate Structural Studies by Cryo-EM and Reveal the Role of the Integrase C-Terminal Tail in HIV-1 Integration

by Min Li, Zhen Li, Xuemin Chen, Yanxiang Cui, Alan N. Engelman and Robert Craigie

Viruses 2024, 16(7), 1166; https://doi.org/10.3390/v16071166 - 20 Jul 2024

Viewed by 1037

Abstract

Retroviral integration is mediated by intasome nucleoprotein complexes wherein a pair of viral DNA ends are bridged together by a multimer of integrase (IN). Atomic-resolution structures of HIV-1 intasomes provide detailed insights into the mechanism of integration and inhibition by clinical IN inhibitors. [...] Read more.

Retroviral integration is mediated by intasome nucleoprotein complexes wherein a pair of viral DNA ends are bridged together by a multimer of integrase (IN). Atomic-resolution structures of HIV-1 intasomes provide detailed insights into the mechanism of integration and inhibition by clinical IN inhibitors. However, previously described HIV-1 intasomes are highly heterogeneous and have the tendency to form stacks, which is a limiting factor in determining high-resolution cryo-EM maps. We have assembled HIV-1 intasomes in the presence of excess IN C-terminal domain protein, which was readily incorporated into the intasomes. The purified intasomes were largely homogeneous and exhibited minimal stacking tendencies. The cryo-EM map resolution was further improved to 2.01 Å, which will greatly facilitate structural studies of IN inhibitor action and drug resistance mechanisms. The C-terminal 18 residues of HIV-1 IN, which are critical for virus replication and integration in vitro, have not been well resolved in previous intasome structures, and its function remains unclear. We show that the C-terminal tail participates in intasome assembly, resides within the intasome core, and forms a small alpha helix (residues 271–276). Mutations that disrupt alpha helix integrity impede IN activity in vitro and disrupt HIV-1 infection at the step of viral DNA integration. Full article

(This article belongs to the Section General Virology)

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16 pages, 595 KiB

Open AccessReview

Epidemiology of Enterovirus Genotypes in Association with Human Diseases

by Zhenfeng Xie, Pattara Khamrin, Niwat Maneekarn and Kattareeya Kumthip

Viruses 2024, 16(7), 1165; https://doi.org/10.3390/v16071165 - 19 Jul 2024

Cited by 2 | Viewed by 1013

Abstract

Enteroviruses (EVs) are well-known causes of a wide range of infectious diseases in infants and young children, ranging from mild illnesses to severe conditions, depending on the virus genotypes and the host’s immunity. Recent advances in molecular surveillance and genotyping tools have identified [...] Read more.

Enteroviruses (EVs) are well-known causes of a wide range of infectious diseases in infants and young children, ranging from mild illnesses to severe conditions, depending on the virus genotypes and the host’s immunity. Recent advances in molecular surveillance and genotyping tools have identified over 116 different human EV genotypes from various types of clinical samples. However, the current knowledge about most of these genotypes, except for those of well-known genotypes like EV-A71 and EV-D68, is still limited due to a lack of comprehensive EV surveillance systems. This limited information makes it difficult to understand the true burden of EV-related diseases globally. Furthermore, the specific EV genotype associated with diseases varies according to country, population group, and study period. The same genotype can exhibit different epidemiological features in different areas. By integrating the data from established EV surveillance systems in the USA, Europe, Japan, and China, in combination with other EV infection studies, we can elaborate a better understanding of the distribution of prevalent EV genotypes and the diseases associated with EV. This review analyzed the data from various EV surveillance databases and explored the EV seroprevalence and the association of specific EV genotypes with human diseases. Full article

(This article belongs to the Special Issue An Update on Enterovirus Research)

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17 pages, 5000 KiB

Open AccessReview

Description of Sheep Pox Outbreak in Spain in 2022–2023: Challenges Found and Lessons Learnt in Relation with Control and Eradication of This Disease

by Cáceres G. Germán, Romero G. Luis, Bonilla G. Sergio, Guerrero C. Fatima, Fernandez M. Manuel, Capilla G. Jaime and Tejero C. Jesús

Viruses 2024, 16(7), 1164; https://doi.org/10.3390/v16071164 - 19 Jul 2024

Viewed by 1056

Abstract

Sheep pox and goat pox are infectious viral diseases that affect ovine and caprine animals and are caused by two viruses of the family Poxviridae, genus Capripoxvirus. Sheep pox has been traditionally endemic in Africa, the Middle East, and several Southeast [...] Read more.

Sheep pox and goat pox are infectious viral diseases that affect ovine and caprine animals and are caused by two viruses of the family Poxviridae, genus Capripoxvirus. Sheep pox has been traditionally endemic in Africa, the Middle East, and several Southeast Asian countries, but it is considered a transboundary disease capable of affecting previously free countries epidemically. It is a disease of compulsory immediate notification to the World Organization for Animal Health (WOAH) and the European Union (EU). On 19 September 2022, the disease reemerged in Spain, which had been free of it since 1968, causing a total of 30 outbreaks until 17 May 2023, when the last outbreak of the disease was reported. The control and eradication measures implemented were those laid down in EU legislation, based on the total stamping out of positive herds, zoning and restriction of movement, and strengthening of biosecurity and passive surveillance. This manuscript describes the outbreak, as well as assesses the challenges and lessons learned in relation to its management, with the aim of helping in the effective management of future outbreaks of this disease. Full article

(This article belongs to the Special Issue Capripox Viruses: A Continuing Transboundary Threat to Animal Health)

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27 pages, 2564 KiB

Open AccessReview

HIV Persistence, Latency, and Cure Approaches: Where Are We Now?

by Tessa C. Chou, Nishad S. Maggirwar and Matthew D. Marsden

Viruses 2024, 16(7), 1163; https://doi.org/10.3390/v16071163 - 19 Jul 2024

Viewed by 2207

Abstract

The latent reservoir remains a major roadblock to curing human immunodeficiency virus (HIV) infection. Currently available antiretroviral therapy (ART) can suppress active HIV replication, reduce viral loads to undetectable levels, and halt disease progression. However, antiretroviral drugs are unable to target cells that [...] Read more.

The latent reservoir remains a major roadblock to curing human immunodeficiency virus (HIV) infection. Currently available antiretroviral therapy (ART) can suppress active HIV replication, reduce viral loads to undetectable levels, and halt disease progression. However, antiretroviral drugs are unable to target cells that are latently infected with HIV, which can seed viral rebound if ART is stopped. Consequently, a major focus of the field is to study the latent viral reservoir and develop safe and effective methods to eliminate it. Here, we provide an overview of the major mechanisms governing the establishment and maintenance of HIV latency, the key challenges posed by latent reservoirs, small animal models utilized to study HIV latency, and contemporary cure approaches. We also discuss ongoing efforts to apply these approaches in combination, with the goal of achieving a safe, effective, and scalable cure for HIV that can be extended to the tens of millions of people with HIV worldwide. Full article

(This article belongs to the Special Issue HIV Reservoirs, Latency, and the Factors Responsible)

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13 pages, 730 KiB

Open AccessArticle

Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir

by Ingrid A. Beck, Ceejay L. Boyce, Marley D. Bishop, Yen L. Vu, Amanda Fung, Sheila Styrchak, Nuttada Panpradist, Barry R. Lutz and Lisa M. Frenkel

Viruses 2024, 16(7), 1162; https://doi.org/10.3390/v16071162 - 19 Jul 2024

Viewed by 885

Abstract

The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point [...] Read more.

The WHO currently recommends dolutegravir (DTG)-based ART for persons living with HIV infection in resource-limited-settings (RLS). To expand access to testing for HIV drug resistance (DR) to DTG in RLS, we developed probes for use in the oligonucleotide ligation assay (OLA)-Simple, a near-point of care HIV DR kit. Genotypic data from clinical trials and case reports were used to determine the mutations in HIV-1 integrase critical to identifying individuals with DTG-resistance at virologic failure of DTG-based ART. Probes to detect G118R, Q148H/K/R, N155H and R263K in HIV-1 subtypes A, B, C, D and CRF01_AE were designed using sequence alignments from the Los Alamos database and validated using 61 clinical samples of HIV-1 subtypes A, B, C, D, CRF01_AE genotyped by PacBio (n = 15) or Sanger (n = 46). Initial OLA probes failed to ligate for 16/244 (6.5%) codons (9 at G118R and 7 at Q148H/K/R). Probes revised to accommodate polymorphisms interfering with ligation at codons G118R and Q148R reduced indeterminates to 3.7% (5 at G118R and 4 at Q148H/K/R) and detected DTG-mutations with a sensitivity of 96.5% and 100% specificity. These OLA DTG resistance probes appear highly sensitive and specific across HIV-1 subtypes common in RLS with high burden of HIV infection. Full article

(This article belongs to the Special Issue Antiviral Resistance Mutations)

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17 pages, 2098 KiB

Open AccessReview

Regulation of Mitochondria-Derived Immune Activation by ‘Antiviral’ TRIM Proteins

by Seeun Oh and Michael A. Mandell

Viruses 2024, 16(7), 1161; https://doi.org/10.3390/v16071161 - 19 Jul 2024

Viewed by 1458

Abstract

Mitochondria are key orchestrators of antiviral responses that serve as platforms for the assembly and activation of innate immune-signaling complexes. In response to viral infection, mitochondria can be triggered to release immune-stimulatory molecules that can boost interferon production. These same molecules can be [...] Read more.

Mitochondria are key orchestrators of antiviral responses that serve as platforms for the assembly and activation of innate immune-signaling complexes. In response to viral infection, mitochondria can be triggered to release immune-stimulatory molecules that can boost interferon production. These same molecules can be released by damaged mitochondria to induce pathogenic, antiviral-like immune responses in the absence of infection. This review explores how members of the tripartite motif-containing (TRIM) protein family, which are recognized for their roles in antiviral defense, regulate mitochondria-based innate immune activation. In antiviral defense, TRIMs are essential components of immune signal transduction pathways and function as directly acting viral restriction factors. TRIMs carry out conceptually similar activities when controlling immune activation related to mitochondria. First, they modulate immune-signaling pathways that can be activated by mitochondrial molecules. Second, they co-ordinate the direct removal of mitochondria and associated immune-activating factors through mitophagy. These insights broaden the scope of TRIM actions in innate immunity and may implicate TRIMs in diseases associated with mitochondria-derived inflammation. Full article

(This article belongs to the Special Issue TRIM Proteins in Antiviral Immunity and Virus Pathogenesis)

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18 pages, 2225 KiB

Open AccessArticle

Discovery of Novel Viruses in Culicoides Biting Midges in Chihuahua, Mexico

by S. Viridiana Laredo-Tiscareño, Javier A. Garza-Hernandez, Chandra S. Tangudu, Wichan Dankaona, Carlos A. Rodríguez-Alarcón, Jaime R. Adame-Gallegos, Erick J. De Luna Santillana, Herón Huerta, Rodolfo Gonzalez-Peña, Alejandra Rivera-Martínez, Ezequiel Rubio-Tabares, Diana M. Beristain-Ruiz and Bradley J. Blitvich

Viruses 2024, 16(7), 1160; https://doi.org/10.3390/v16071160 - 19 Jul 2024

Viewed by 1247

Abstract

Biting midges (Culicoides) are vectors of many pathogens of medical and veterinary importance, but their viromes are poorly characterized compared to certain other hematophagous arthropods, e.g., mosquitoes and ticks. The goal of this study was to use metagenomics to identify viruses [...] Read more.

Biting midges (Culicoides) are vectors of many pathogens of medical and veterinary importance, but their viromes are poorly characterized compared to certain other hematophagous arthropods, e.g., mosquitoes and ticks. The goal of this study was to use metagenomics to identify viruses in Culicoides from Mexico. A total of 457 adult midges were collected in Chihuahua, northern Mexico, in 2020 and 2021, and all were identified as female Culicoides reevesi. The midges were sorted into five pools and homogenized. An aliquot of each homogenate was subjected to polyethylene glycol precipitation to enrich for virions, then total RNA was extracted and analyzed by unbiased high-throughput sequencing. We identified six novel viruses that are characteristic of viruses from five families (Nodaviridae, Partitiviridae, Solemoviridae, Tombusviridae, and Totiviridae) and one novel virus that is too divergent from all classified viruses to be assigned to an established family. The newly discovered viruses are phylogenetically distinct from their closest known relatives, and their minimal infection rates in female C. reevesi range from 0.22 to 1.09. No previously known viruses were detected, presumably because viral metagenomics had never before been used to study Culicoides from the Western Hemisphere. To conclude, we discovered multiple novel viruses in C. reevesi from Mexico, expanding our knowledge of arthropod viral diversity and evolution. Full article

(This article belongs to the Section Invertebrate Viruses)

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10 pages, 1065 KiB

Open AccessArticle

Detection of Enteric Viruses in Children under Five Years of Age before and after Rotavirus Vaccine Introduction in Manhiça District, Southern Mozambique, 2008–2019

by Percina Chirinda, Filomena Manjate, Marcelino Garrine, Augusto Messa, Jr., Nélio Nobela, Delfino Vubil, Tacilta Nhampossa, Sozinho Acácio, Quique Bassat, Karen L. Kotloff, Myron M. Levine, James P. Nataro, Jacqueline E. Tate, Umesh Parashar, Jason M. Mwenda, Pedro L. Alonso, Eva D. João and Inácio Mandomando

Viruses 2024, 16(7), 1159; https://doi.org/10.3390/v16071159 - 18 Jul 2024

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Abstract

Enteric viruses are the leading cause of diarrhoea in children <5 years. Despite existing studies describing rotavirus diarrhoea in Mozambique, data on other enteric viruses remains scarce, especially after rotavirus vaccine introduction. We explored the prevalence of norovirus GI and GII, adenovirus 40/41, [...] Read more.

Enteric viruses are the leading cause of diarrhoea in children <5 years. Despite existing studies describing rotavirus diarrhoea in Mozambique, data on other enteric viruses remains scarce, especially after rotavirus vaccine introduction. We explored the prevalence of norovirus GI and GII, adenovirus 40/41, astrovirus, and sapovirus in children <5 years with moderate-to-severe (MSD), less severe (LSD) diarrhoea and community healthy controls, before (2008–2012) and after (2016–2019) rotavirus vaccine introduction in Manhiça District, Mozambique. The viruses were detected using ELISA and conventional reverse transcription PCR from stool samples. Overall, all of the viruses except norovirus GI were significantly more detected after rotavirus vaccine introduction compared to the period before vaccine introduction: norovirus GII in MSD (13/195, 6.7% vs. 24/886, 2.7%, respectively; p = 0.006) and LSD (25/268, 9.3% vs. 9/430, 2.1%, p < 0.001); adenovirus 40/41 in MSD (7.2% vs. 1.8%, p < 0.001); astrovirus in LSD (7.5% vs. 2.6%, p = 0.002); and sapovirus in MSD (7.1% vs. 1.4%, p = 0.047) and controls (21/475, 4.4% vs. 51/2380, 2.1%, p = 0.004). Norovirus GII, adenovirus 40/41, astrovirus, and sapovirus detection increased in MSD and LSD cases after rotavirus vaccine introduction, supporting the need for continued molecular surveillance for the implementation of appropriate control and prevention measures. Full article

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

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22 pages, 3562 KiB

Open AccessArticle

Novel Pan-Coronavirus 3CL Protease Inhibitor MK-7845: Biological and Pharmacological Profiling

by Nadine Alvarez, Gregory C. Adam, John A. Howe, Vijeta Sharma, Matthew D. Zimmerman, Enriko Dolgov, Risha Rasheed, Fatima Nizar, Khushboo Sahay, Andrew M. Nelson, Steven Park, Xiaoyan Zhou, Christine Burlein, John F. Fay, Daniel V. Iwamoto, Carolyn M. Bahnck-Teets, Krista L. Getty, Shih Lin Goh, Imad Salhab, Keith Smith, Christopher W. Boyce, Tamara D. Cabalu, Nicholas Murgolo, Nicholas G. Fox, Todd W. Mayhood, Valerie W. Shurtleff, Mark E. Layton, Craig A. Parish, John A. McCauley, David B. Olsen and David S. Perlin Show full author list Hide full author list

Viruses 2024, 16(7), 1158; https://doi.org/10.3390/v16071158 - 18 Jul 2024

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Abstract

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as [...] Read more.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC), which first emerged in 2012, persist and continue to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After the extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction in viral burdens by >6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice). Full article

(This article belongs to the Special Issue Viral Replication Inhibitors)

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11 pages, 1044 KiB

Open AccessArticle

The Transmission of SARS-CoV-2 from COVID-19-Diagnosed People to Their Pet Dogs and Cats in a Multi-Year Surveillance Project

by Anne K. Kimmerlein, Talon S. McKee, Philip J. Bergman, Irina Sokolchik and Christian M. Leutenegger

Viruses 2024, 16(7), 1157; https://doi.org/10.3390/v16071157 - 18 Jul 2024

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Abstract

Recent emerging zoonotic disease outbreaks, such as that of SARS-CoV-2, have demonstrated the need for wider companion animal disease surveillance. We tested 1000 dogs and cats belonging to employees of a US veterinary hospital network that were exposed to human COVID-19 cases in [...] Read more.

Recent emerging zoonotic disease outbreaks, such as that of SARS-CoV-2, have demonstrated the need for wider companion animal disease surveillance. We tested 1000 dogs and cats belonging to employees of a US veterinary hospital network that were exposed to human COVID-19 cases in the household between 1 January 2020 and 10 March 2022 for SARS-CoV-2 and surveyed their owners about clinical signs and risk factors. The seropositivity was 33% for 747 dogs and 27% for 253 cats. Pet seropositivity correlated with the US human case rates over time, exhibiting peaks corresponding with the major COVID-19 surges. Antibodies persisted longer than previously documented (828 days in dogs; 650 days in cats). Increasing age and duration of proximity to infected people were associated with increased seropositivity in dogs but not cats. Cats were more likely to have clinical signs, but an association between seropositivity and the presence of clinical signs was not found in either species. Full article

(This article belongs to the Section Coronaviruses)

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22 pages, 3083 KiB

Open AccessArticle

A Marek’s Disease Virus Messenger RNA-Based Vaccine Modulates Local and Systemic Immune Responses in Chickens

by Fatemeh Fazel, Ayumi Matsuyama-Kato, Mohammadali Alizadeh, Jiayu Zheng, Charlotte Fletcher, Bhavya Gupta, Myles St-Denis, Nitish Boodhoo and Shayan Sharif

Viruses 2024, 16(7), 1156; https://doi.org/10.3390/v16071156 - 18 Jul 2024

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Abstract

Marek’s disease (MD), caused by the Marek’s disease virus, is a lymphoproliferative disease in chickens that can be controlled by vaccination. However, the current vaccines can limit tumor growth and death but not virus replication and transmission. The present study aimed to evaluate [...] Read more.

Marek’s disease (MD), caused by the Marek’s disease virus, is a lymphoproliferative disease in chickens that can be controlled by vaccination. However, the current vaccines can limit tumor growth and death but not virus replication and transmission. The present study aimed to evaluate host responses following intramuscular injection of an mRNA vaccine encoding gB and pp38 proteins of the MDV within the first 36 h. The vaccine was injected in low and high doses using prime and prime-boost strategies. The expression of type I and II interferons (IFNs), a panel of interferon-stimulated genes, and two key antiviral cytokines, IL-1β and IL-2, were measured in spleen and lungs after vaccination. The transcriptional analysis of the above genes showed significant increases in the expression of MDA5, Myd88, IFN-α, IFN-β, IFN-γ, IRF7, OAS, Mx1, and IL-2 in both the spleen and lungs within the first 36 h of immunization. Secondary immunization increased expression of all the above genes in the lungs. In contrast, only IFN-γ, MDA5, MyD88, Mx1, and OAS showed significant upregulation in the spleen after the secondary immunization. This study shows that two doses of the MDV mRNA vaccine encoding gB and pp38 antigens activate innate and adaptive responses and induce an antiviral state in chickens. Full article

(This article belongs to the Special Issue Marek's Disease Virus)

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16 pages, 2270 KiB

Open AccessArticle

Development of Stabilizing Solution for Long-Term Storage of Bacteriophages at Room Temperature and Application to Control Foodborne Pathogens

by Eo-Jin Kim, Min-Cheol Lim, Min-Ah Woo, Byoung Sik Kim and Jeong-A Lim

Viruses 2024, 16(7), 1155; https://doi.org/10.3390/v16071155 - 17 Jul 2024

Viewed by 1184

Abstract

Bacteriophages (phages) have gained considerable attention as effective antimicrobial agents that infect and kill pathogenic bacteria. Based on this feature, phages have been increasingly used to achieve food safety. They are stored in a medium or buffer to ensure stability; however, they cannot [...] Read more.

Bacteriophages (phages) have gained considerable attention as effective antimicrobial agents that infect and kill pathogenic bacteria. Based on this feature, phages have been increasingly used to achieve food safety. They are stored in a medium or buffer to ensure stability; however, they cannot be directly applied to food under these conditions due to reasons such as regulatory considerations and concerns about marketability. This study developed a stabilizing solution that allowed the maintenance of phage activity for extended periods at room temperature while being directly applicable to food. The stability of phages stored in distilled water was relatively low. However, adding a stabilizer composed of sugars and salts improved the survival rates of phages significantly, resulting in stability for up to 48 weeks at room temperature. When Escherichia coli O157:H7-contaminated vegetables were washed with tap water containing phages, the phages reduced the pathogenic E. coli count by over 90% compared with washing with tap water alone. Additionally, when pathogenic E. coli-contaminated vegetables were placed in a phage-coated container and exposed to water, the coating of the container dissolved, releasing phages and lysing the pathogenic E. coli. This led to a significant 90% reduction in pathogenic E. coli contamination compared to that after water rinsing. These results suggest an effective and economical method for maintaining phage activity and establishing the potential for commercialization through application in the food industry. Full article

(This article belongs to the Section Bacterial Viruses)

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16 pages, 4678 KiB

Open AccessArticle

Hantavirus Expansion Trends in Natural Host Populations in Brazil

by José Henrique Fortes Mello, Renata L. Muylaert and Carlos Eduardo Viveiros Grelle

Viruses 2024, 16(7), 1154; https://doi.org/10.3390/v16071154 - 17 Jul 2024

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Abstract

Hantaviruses are zoonotic agents responsible for causing Hantavirus Cardiopulmonary Syndrome (HCPS) in the Americas, with Brazil ranking first in number of confirmed HCPS cases in South America. In this study, we simulate the monthly spread of highly lethal hantavirus in natural hosts by [...] Read more.

Hantaviruses are zoonotic agents responsible for causing Hantavirus Cardiopulmonary Syndrome (HCPS) in the Americas, with Brazil ranking first in number of confirmed HCPS cases in South America. In this study, we simulate the monthly spread of highly lethal hantavirus in natural hosts by conjugating a Kermack–McCormick SIR model with a cellular automata model (CA), therefore simultaneously evaluating both in-cell and between-cell infection dynamics in host populations, using recently compiled data on main host species abundances and confirmed deaths by hantavirus infection. For both host species, our models predict an increase in the area of infection, with 22 municipalities where no cases have been confirmed to date expected to have at least one case in the next decade, and a reduction in infection in 11 municipalities. Our findings support existing research and reveal new areas where hantavirus is likely to spread within recognized epicenters. Highlighting spatial-temporal trends and potential expansion, we emphasize the increased risk due to pervasive habitat fragmentation and agricultural expansion. Consistent prevention efforts and One Health actions are crucial, especially in newly identified high-risk municipalities. Full article

(This article belongs to the Special Issue Bat- and Rodent-Borne Zoonotic Viruses)

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18 pages, 4246 KiB

Open AccessArticle

The Oncolytic Avian Reovirus p17 Protein Inhibits Invadopodia Formation in Murine Melanoma Cancer Cells by Suppressing the FAK/Src Pathway and the Formation of theTKs5/NCK1 Complex

by Chao-Yu Hsu, Jyun-Yi Li, En-Ying Yang, Tsai-Ling Liao, Hsiao-Wei Wen, Pei-Chien Tsai, Tz-Chuen Ju, Lon-Fye Lye, Brent L. Nielsen and Hung-Jen Liu

Viruses 2024, 16(7), 1153; https://doi.org/10.3390/v16071153 - 17 Jul 2024

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Abstract

To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog [...] Read more.

To explore whether the p17 protein of oncolytic avian reovirus (ARV) mediates cell migration and invadopodia formation, we applied several molecular biological approaches for studying the involved cellular factors and signal pathways. We found that ARV p17 activates the p53/phosphatase and tensin homolog (PTEN) pathway to suppress the focal adhesion kinase (FAK)/Src signaling and downstream signal molecules, thus inhibiting cell migration and the formation of invadopodia in murine melanoma cancer cell line (B16-F10). Importantly, p17-induced formation of invadopodia could be reversed in cells transfected with the mutant PTEN_C124A. p17 protein was found to significantly reduce the expression levels of tyrosine kinase substrate 5 (TKs5), Rab40b, non-catalytic region of tyrosine kinase adaptor protein 1 (NCK1), and matrix metalloproteinases (MMP9), suggesting that TKs5 and Rab40b were transcriptionally downregulated by p17. Furthermore, we found that p17 suppresses the formation of the TKs5/NCK1 complex. Coexpression of TKs5 and Rab40b in B16-F10 cancer cells reversed p17-modulated suppression of the formation of invadopodia. This work provides new insights into p17-modulated suppression of invadopodia formation by activating the p53/PTEN pathway, suppressing the FAK/Src pathway, and inhibiting the formation of the TKs5/NCK1 complex. Full article

(This article belongs to the Special Issue Recent Advances of Avian Viruses Research)

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22 pages, 7509 KiB

Open AccessArticle

Metatranscriptomic Sequencing of Sheath Blight-Associated Isolates of Rhizoctonia solani Revealed Multi-Infection by Diverse Groups of RNA Viruses

by Michael Louie R. Urzo, Timothy D. Guinto, Ana Eusebio-Cope, Bernard O. Budot, Mary Jeanie T. Yanoria, Gilda B. Jonson, Masao Arakawa, Hideki Kondo and Nobuhiro Suzuki

Viruses 2024, 16(7), 1152; https://doi.org/10.3390/v16071152 - 17 Jul 2024

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Abstract

Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements [...] Read more.

Rice sheath blight, caused by the soil-borne fungus Rhizoctonia solani (teleomorph: Thanatephorus cucumeris, Basidiomycota), is one of the most devastating phytopathogenic fungal diseases and causes yield loss. Here, we report on a very high prevalence (100%) of potential virus-associated double-stranded RNA (dsRNA) elements for a collection of 39 fungal strains of R. solani from the rice sheath blight samples from at least four major rice-growing areas in the Philippines and a reference isolate from the International Rice Research Institute, showing different colony phenotypes. Their dsRNA profiles suggested the presence of multiple viral infections among these Philippine R. solani populations. Using next-generation sequencing, the viral sequences of the three representative R. solani strains (Ilo-Rs-6, Tar-Rs-3, and Tar-Rs-5) from different rice-growing areas revealed the presence of at least 36 viruses or virus-like agents, with the Tar-Rs-3 strain harboring the largest number of viruses (at least 20 in total). These mycoviruses or their candidates are believed to have single-stranded RNA or dsRNA genomes and they belong to or are associated with the orders Martellivirales, Hepelivirales, Durnavirales, Cryppavirales, Ourlivirales, and Ghabrivirales based on their coding-complete RNA-dependent RNA polymerase sequences. The complete genome sequences of two novel RNA viruses belonging to the proposed family Phlegiviridae and family Mitoviridae were determined. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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14 pages, 2793 KiB

Open AccessArticle

Rupestonic Acid Derivative YZH-106 Promotes Lysosomal Degradation of HBV L- and M-HBsAg via Direct Interaction with PreS2 Domain

by Lanlan Liu, Haoyu Wang, Lulu Liu, Fang Cheng, Haji Akber Aisa, Changfei Li and Songdong Meng

Viruses 2024, 16(7), 1151; https://doi.org/10.3390/v16071151 - 17 Jul 2024

Viewed by 651

Abstract

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but it also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg [...] Read more.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but it also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for an HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. A mechanistic study using Biacore and docking analysis revealed that YZH-106 bound directly to the PreS2 domain of L- and M-HBsAg, thereby blocking their entry into the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provides the basis for the design of a novel compound therapy to target HBsAg against HBV infection. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Clinical Manifestations of Persistent Viral Infections)

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13 pages, 4882 KiB

Open AccessArticle

Impact of Missense Mutations on Spike Protein Stability and Binding Affinity in the Omicron Variant

by Vidhyanand Mahase, Adebiyi Sobitan, Qiaobin Yao, Xinghua Shi, Hong Qin, Dawit Kidane, Qiyi Tang and Shaolei Teng

Viruses 2024, 16(7), 1150; https://doi.org/10.3390/v16071150 - 17 Jul 2024

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Abstract

The global effort to combat the COVID-19 pandemic faces ongoing uncertainty with the emergence of Variants of Concern featuring numerous mutations on the Spike (S) protein. In particular, the Omicron Variant is distinguished by 32 mutations, including 10 within its receptor-binding domain (RBD). [...] Read more.

The global effort to combat the COVID-19 pandemic faces ongoing uncertainty with the emergence of Variants of Concern featuring numerous mutations on the Spike (S) protein. In particular, the Omicron Variant is distinguished by 32 mutations, including 10 within its receptor-binding domain (RBD). These mutations significantly impact viral infectivity and the efficacy of vaccines and antibodies currently in use for therapeutic purposes. In our study, we employed structure-based computational saturation mutagenesis approaches to predict the effects of Omicron missense mutations on RBD stability and binding affinity, comparing them to the original Wuhan-Hu-1 strain. Our results predict that mutations such as G431W and P507W induce the most substantial destabilizations in the Wuhan-Hu-1-S/Omicron-S RBD. Notably, we postulate that mutations in the Omicron-S exhibit a higher percentage of enhancing binding affinity compared to Wuhan-S. We found that the mutations at residue positions G447, Y449, F456, F486, and S496 led to significant changes in binding affinity. In summary, our findings may shed light on the widespread prevalence of Omicron mutations in human populations. The Omicron mutations that potentially enhance their affinity for human receptors may facilitate increased viral binding and internalization in infected cells, thereby enhancing infectivity. This informs the development of new neutralizing antibodies capable of targeting Omicron’s immune-evading mutations, potentially aiding in the ongoing battle against the COVID-19 pandemic. Full article

(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus)

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5 pages, 869 KiB

Open AccessBrief Report

The Rare Condition of a Double Cervix: Results from the High-Risk Human Papillomavirus-Based Cervical Cancer Screening Program in the Lazio Region

by Tiziana Pisani, Ettore Domenico Capoluongo and Maria Cenci

Viruses 2024, 16(7), 1149; https://doi.org/10.3390/v16071149 - 17 Jul 2024

Viewed by 685

Abstract

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation [...] Read more.

Precancerous and cancerous lesions of the uterine cervix are known to be associated with Human Papillomavirus (HPV) infection. The screening of high-risk (HR)-HPV infection in the female population has led to the discovery of several cases of a double cervix, a congenital malformation that is very rare. The purpose of this study was to evaluate HR-HPV infections in women with a double cervix within the National Cervical Cancer Screening program of the Lazio region (Italy). From June 2021 to March 2024, a total of 142,437 samples were analyzed by Seegene’s Anyplex TM II HR-HPV method, which identifies 14 HR-HPV genotypes. For each woman identified with a double cervix, two separate samples were taken from both cervices and analyzed separately. Twenty-seven women with a double cervix were identified (0.019%): 23 women were tested as negative for both cervices, while the remaining four (namely A, B, C, and D) resulted positive. By genotyping, the following results were obtained: (A) Both samples showed genotype 31; (B) one cervix was negative while the other showed genotype 58; (C) one cervix was positive for HPV 18 and 31 while for 18, 31, and 33 in the other; and (D) one cervix showed genotype 66 while the other carried the 66 and 68 genotypes. Double cervix is a very rare condition where the presence of HR-HPV genotypes is not homogeneous. As already described, our study confirms that different genotypes can be detected in double cervix malformation, suggesting the need to perform HPV screening on brushing samples from both cervices. Full article

(This article belongs to the Special Issue HPV-Associated Cancers)

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16 pages, 7075 KiB

Open AccessArticle

Genomic Epidemiology of Rift Valley Fever Virus Involved in the 2018 and 2022 Outbreaks in Livestock in Rwanda

by Isidore Nsengimana, John Juma, Kristina Roesel, Methode N. Gasana, Fabrice Ndayisenga, Claude M. Muvunyi, Emmanuel Hakizimana, Jean N. Hakizimana, Gillian Eastwood, Augustino A. Chengula, Bernard Bett, Christopher J. Kasanga and Samuel O. Oyola

Viruses 2024, 16(7), 1148; https://doi.org/10.3390/v16071148 - 17 Jul 2024

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Abstract

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one [...] Read more.

Rift Valley fever (RVF), a mosquito-borne transboundary zoonosis, was first confirmed in Rwanda’s livestock in 2012 and since then sporadic cases have been reported almost every year. In 2018, the country experienced its first large outbreak, which was followed by a second one in 2022. To determine the circulating virus lineages and their ancestral origin, two genome sequences from the 2018 outbreak, and thirty-six, forty-one, and thirty-eight sequences of small (S), medium (M), and large (L) genome segments, respectively, from the 2022 outbreak were generated. All of the samples from the 2022 outbreak were collected from slaughterhouses. Both maximum likelihood and Bayesian-based phylogenetic analyses were performed. The findings showed that RVF viruses belonging to a single lineage, C, were circulating during the two outbreaks, and shared a recent common ancestor with RVF viruses isolated in Uganda between 2016 and 2019, and were also linked to the 2006/2007 largest East Africa RVF outbreak reported in Kenya, Tanzania, and Somalia. Alongside the wild-type viruses, genetic evidence of the RVFV Clone 13 vaccine strain was found in slaughterhouse animals, demonstrating a possible occupational risk of exposure with unknown outcome for people working in meat-related industry. These results provide additional evidence of the ongoing wide spread of RVFV lineage C in Africa and emphasize the need for an effective national and international One Health-based collaborative approach in responding to RVF emergencies. Full article

(This article belongs to the Special Issue Emerging Highlights in the Study of Rift Valley Fever Virus)

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15 pages, 2577 KiB

Open AccessArticle

Evaluating the Impact of Low-Pathogenicity Avian Influenza H6N1 Outbreaks in United Kingdom and Republic of Ireland Poultry Farms during 2020

by Michael J. McMenamy, Robyn McKenna, Valerie B. Bailie, Ben Cunningham, Adam Jeffers, Kelly McCullough, Catherine Forsythe, Laura Garza Cuartero, Orla Flynn, Christina Byrne, Emily Connaghan, John Moriarty, June Fanning, Stephanie Ronan, Damien Barrett, Alice Fusaro, Isabella Monne, Calogero Terregino, Joe James, Alexander M. P. Byrne, Fabian Z. X. Lean, Alejandro Núñez, Scott M. Reid, Rowena Hansen, Ian H. Brown, Ashley C. Banyard and Ken Lemon Show full author list Hide full author list

Viruses 2024, 16(7), 1147; https://doi.org/10.3390/v16071147 - 16 Jul 2024

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Abstract

In January 2020, increased mortality was reported in a small broiler breeder flock in County Fermanagh, Northern Ireland. Gross pathological findings included coelomitis, oophoritis, salpingitis, visceral gout, splenomegaly, and renomegaly. Clinical presentation included inappetence, pronounced diarrhoea, and increased egg deformation. These signs, in [...] Read more.

In January 2020, increased mortality was reported in a small broiler breeder flock in County Fermanagh, Northern Ireland. Gross pathological findings included coelomitis, oophoritis, salpingitis, visceral gout, splenomegaly, and renomegaly. Clinical presentation included inappetence, pronounced diarrhoea, and increased egg deformation. These signs, in combination with increased mortality, triggered a notifiable avian disease investigation. High pathogenicity avian influenza virus (HPAIV) was not suspected, as mortality levels and clinical signs were not consistent with HPAIV. Laboratory investigation demonstrated the causative agent to be a low-pathogenicity avian influenza virus (LPAIV), subtype H6N1, resulting in an outbreak that affected 15 premises in Northern Ireland. The H6N1 virus was also associated with infection on 13 premises in the Republic of Ireland and six in Great Britain. The close genetic relationship between the viruses in Ireland and Northern Ireland suggested a direct causal link whereas those in Great Britain were associated with exposure to a common ancestral virus. Overall, this rapidly spreading outbreak required the culling of over 2 million birds across the United Kingdom and the Republic of Ireland to stamp out the incursion. This report demonstrates the importance of investigating LPAIV outbreaks promptly, given their substantial economic impacts. Full article

(This article belongs to the Special Issue Filling Knowledge Gaps: Understanding the Impact of Low Pathogenicity Avian Influenza Viruses and Their Role in Novel Virus Emergence)

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17 pages, 9137 KiB

Open AccessArticle

Characterization of Six Ampeloviruses Infecting Pineapple in Reunion Island Using a Combination of High-Throughput Sequencing Approaches

by Delphine Massé, Thierry Candresse, Denis Filloux, Sébastien Massart, Nathalie Cassam, Bruno Hostachy, Armelle Marais, Emmanuel Fernandez, Philippe Roumagnac, Eric Verdin, Pierre-Yves Teycheney, Jean-Michel Lett and Pierre Lefeuvre

Viruses 2024, 16(7), 1146; https://doi.org/10.3390/v16071146 - 16 Jul 2024

Viewed by 725

Abstract

The cultivation of pineapple (Ananas comosus) is threatened worldwide by mealybug wilt disease of pineapple (MWP), whose etiology is not yet fully elucidated. In this study, we characterized pineapple mealybug wilt-associated ampeloviruses (PMWaVs, family Closteroviridae) from a diseased pineapple plant [...] Read more.

The cultivation of pineapple (Ananas comosus) is threatened worldwide by mealybug wilt disease of pineapple (MWP), whose etiology is not yet fully elucidated. In this study, we characterized pineapple mealybug wilt-associated ampeloviruses (PMWaVs, family Closteroviridae) from a diseased pineapple plant collected from Reunion Island, using a high-throughput sequencing approach combining Illumina short reads and Nanopore long reads. Reads co-assembly resulted in complete or near-complete genomes for six distinct ampeloviruses, including the first complete genome of pineapple mealybug wilt-associated virus 5 (PMWaV5) and that of a new species tentatively named pineapple mealybug wilt-associated virus 7 (PMWaV7). Short reads data provided high genome coverage and sequencing depths for all six viral genomes, contrary to long reads data. The 5′ and 3′ ends of the genome for most of the six ampeloviruses could be recovered from long reads, providing an alternative to RACE-PCRs. Phylogenetic analyses did not unveil any geographic structuring of the diversity of PMWaV1, PMWaV2 and PMWaV3 isolates, supporting the current hypothesis that PMWaVs were mainly spread by human activity and vegetative propagation. Full article

(This article belongs to the Section Viruses of Plants, Fungi and Protozoa)

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14 pages, 1833 KiB

Open AccessArticle

Chimeric Viruses Enable Study of Antibody Responses to Human Rotaviruses in Mice

by Sarah Woodyear, Tawny L. Chandler, Takahiro Kawagishi, Tom M. Lonergan, Vanshika A. Patel, Caitlin A. Williams, Sallie R. Permar, Siyuan Ding and Sarah L. Caddy

Viruses 2024, 16(7), 1145; https://doi.org/10.3390/v16071145 - 16 Jul 2024

Viewed by 1145

Abstract

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have [...] Read more.

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human-rotavirus-specific immunity to the outer capsid, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics. Full article

(This article belongs to the Special Issue Rotaviruses and Rotavirus Vaccines)

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Viruses, Volume 16, Issue 7 (July 2024) – 178 articles

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