Molecular and Therapeutic Aspects of Viral Infections

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Virology".

Deadline for manuscript submissions: closed (15 July 2021) | Viewed by 12066

Special Issue Editor


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Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: virus evolution; macrophages; HIV pathogenesis; antivirals; HIV chemotherapy; microbicides; viral resistance; neuroAIDS; mechanisms of virus entry; chemokines and chemokine receptors; role of astrocytes and neurons in HIV infection
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Special Issue Information

Dear Colleagues,

Pathogenic microorganisms, such as bacteria, viruses, parasites, or fungi can cause infectious diseases and can be spread, directly or indirectly, from one person to another. Among infectious diseases, viral infections cause several serious human diseases with high mortality rates. The molecular aspect of drug-resistant viral evolution needs to be better investigated. Indeed, the emergence of new resistant strains, due to the high viral mutation rate, prompts the development of new potent antiviral compounds and therapeutic approaches. All researchers working in the fields of human viral infections and antiviral drugs are cordially invited to contribute original research papers or reviews to this Special Issue of Microorganisms.

Prof. Stefano Aquaro
Guest Editor

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Keywords

  • Viruses
  • Virus pathogenesis
  • Antivirals
  • Drug design
  • Antiviral activity
  • Antiviral resistance
  • Virus evolution
  • Antiviral therapy
  • Virus entry
  • Virus replication
  • Viral enzymes

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Published Papers (4 papers)

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Research

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17 pages, 2231 KiB  
Article
Phylogenetic and Phylodynamic Analyses of HCV Strains Circulating among Patients Using Injectable Drugs in Central Italy
by Claudia Minosse, Leonidas Salichos, Chiara Taibi, Ilaria Luzzitelli, Daniela Nardozi, Maria Rosaria Capobianchi, Gianpiero D’Offizi, Fiona McPhee and Anna Rosa Garbuglia
Microorganisms 2021, 9(7), 1432; https://doi.org/10.3390/microorganisms9071432 - 2 Jul 2021
Cited by 3 | Viewed by 2688
Abstract
Approximately 71 million people worldwide are infected with the hepatitis C virus (HCV). Injectable drug use represents the most common route of transmission in Europe and other developed countries. We studied the molecular characteristics of the HCV infection among mono-infected people who used [...] Read more.
Approximately 71 million people worldwide are infected with the hepatitis C virus (HCV). Injectable drug use represents the most common route of transmission in Europe and other developed countries. We studied the molecular characteristics of the HCV infection among mono-infected people who used drugs (PWUD) in Italy. Among 208 PWUD with anti-HCV antibodies, 101 (48.6%) were HCV RNA-positive, the majority (47%) were infected with the HCV genotype (Gt)1a, followed by Gt3a (34.9%), Gt4 (9.1%), Gt1b (4.5%), and Gt2 (4.5%). Bayesian phylogenetic analyses of clustered HCV NS5B sequences from 66 HCV-positive PWUDs with available plasma samples indicated age and neighborhood proximity as the most common characteristics between closely related HCV strains. Population dynamics, as measured by a coalescent Bayesian skyline analysis, revealed an increase in HCV Gt1a infections from the mid-1980s to mid-1990s. While HCV Gt3a infections were first detected in the 1980s, patient numbers with this genotype subtype remained relatively constant. For both Gt1a and Gt3a, Birth–Death Bayesian Skyline analyses produced higher reproduction numbers post 2014. For earlier time intervals, slow growths were observed for both Gt1a and Gt3a with reproduction numbers (Re) of approximately 1. The evolutionary rates for Gt1a and Gt3a were estimated as 2.23 × 10−4 and 3.85 × 10−4, respectively. Full article
(This article belongs to the Special Issue Molecular and Therapeutic Aspects of Viral Infections)
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10 pages, 602 KiB  
Article
An Increase in the Levels of Middle Surface Antigen Characterizes Patients Developing HBV-Driven Liver Cancer Despite Prolonged Virological Suppression
by Giuseppina Brancaccio, Romina Salpini, Lorenzo Piermatteo, Matteo Surdo, Vanessa Fini, Luna Colagrossi, Marco Cantone, Arianna Battisti, Yasunori Oda, Domenico Di Carlo, Francesca Ceccherini-Silberstein, Carlo Federico Perno, Giovanni Battista Gaeta and Valentina Svicher
Microorganisms 2021, 9(4), 752; https://doi.org/10.3390/microorganisms9040752 - 2 Apr 2021
Cited by 12 | Viewed by 2070
Abstract
Hepatitis B virus (HBV) contains three surface glycoproteins—Large-HBs (L-HBs), Middle-HBs (M-HBs), and Small-HBs (S-HBs), known to contribute to HBV-driven pro-oncogenic properties. Here, we examined the kinetics of HBs-isoforms in virologically-suppressed patients who developed or did not develop hepatocellular carcinoma (HCC). This study enrolled [...] Read more.
Hepatitis B virus (HBV) contains three surface glycoproteins—Large-HBs (L-HBs), Middle-HBs (M-HBs), and Small-HBs (S-HBs), known to contribute to HBV-driven pro-oncogenic properties. Here, we examined the kinetics of HBs-isoforms in virologically-suppressed patients who developed or did not develop hepatocellular carcinoma (HCC). This study enrolled 30 chronically HBV-infected cirrhotic patients under fully-suppressive anti-HBV treatment. Among them, 13 patients developed HCC. Serum samples were collected at enrolment (T0) and at HCC diagnosis or at the last control for non-HCC patients (median (range) follow-up: 38 (12–48) months). Ad-hoc ELISAs were designed to quantify L-HBs, M-HBs and S-HBs (Beacle). At T0, median (IQR) levels of S-HBs, M-HBs and L-HBs were 3140 (457–6995), 220 (31–433) and 0.2 (0–1.7) ng/mL. No significant differences in the fraction of the three HBs-isoforms were noticed between patients who developed or did not develop HCC at T0. On treatment, S-HBs showed a >25% decline or remained stable in a similar proportion of HCC and non-HCC patients (58.3% of HCC- vs. 47.1% of non-HCC patients, p = 0.6; 25% of HCC vs. 29.4% of non-HCC, p = 0.8, respectively). Conversely, M-HBs showed a >25% increase in a higher proportion of HCC compared to non-HCC patients (50% vs. 11.8%, p = 0.02), in line with M-HBs pro-oncogenic role reported in in vitro studies. No difference in L-HBs kinetics was observed in HCC and non-HCC patients. In conclusion, an increase in M-HBs levels characterizes a significant fraction of HCC-patients while under prolonged HBV suppression and stable/reduced total-HBs. The role of M-HBs kinetics in identifying patients at higher HCC risk deserves further investigation. Full article
(This article belongs to the Special Issue Molecular and Therapeutic Aspects of Viral Infections)
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Review

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22 pages, 10298 KiB  
Review
Crucial Role of Central Nervous System as a Viral Anatomical Compartment for HIV-1 Infection
by Ana Borrajo, Valentina Svicher, Romina Salpini, Michele Pellegrino and Stefano Aquaro
Microorganisms 2021, 9(12), 2537; https://doi.org/10.3390/microorganisms9122537 - 8 Dec 2021
Cited by 9 | Viewed by 3050
Abstract
The chronic infection established by the human immunodeficiency virus 1 (HIV-1) produces serious CD4+ T cell immunodeficiency despite the decrease in HIV-1 ribonucleic acid (RNA) levels and the raised life expectancy of people living with HIV-1 (PLWH) through treatment with combined antiretroviral therapies [...] Read more.
The chronic infection established by the human immunodeficiency virus 1 (HIV-1) produces serious CD4+ T cell immunodeficiency despite the decrease in HIV-1 ribonucleic acid (RNA) levels and the raised life expectancy of people living with HIV-1 (PLWH) through treatment with combined antiretroviral therapies (cART). HIV-1 enters the central nervous system (CNS), where perivascular macrophages and microglia are infected. Serious neurodegenerative symptoms related to HIV-associated neurocognitive disorders (HAND) are produced by infection of the CNS. Despite advances in the treatment of this infection, HAND significantly contribute to morbidity and mortality globally. The pathogenesis and the role of inflammation in HAND are still incompletely understood. Principally, growing evidence shows that the CNS is an anatomical reservoir for viral infection and replication, and that its compartmentalization can trigger the evolution of neurological damage and thus make virus eradication more difficult. In this review, important concepts for understanding HAND and neuropathogenesis as well as the viral proteins involved in the CNS as an anatomical reservoir for HIV infection are discussed. In addition, an overview of the recent advancements towards therapeutic strategies for the treatment of HAND is presented. Further neurological research is needed to address neurodegenerative difficulties in people living with HIV, specifically regarding CNS viral reservoirs and their effects on eradication. Full article
(This article belongs to the Special Issue Molecular and Therapeutic Aspects of Viral Infections)
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Other

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7 pages, 1354 KiB  
Case Report
Combined Therapy with Intravenous Immunoglobulins, Letermovir and (Val-)Ganciclovir in Complicated Courses of CMV-Infection in Transplant Recipients
by Veronica Di Cristanziano, Patrick Affeldt, Moritz Trappe, Maike Wirtz, Eva Heger, Elena Knops, Rolf Kaiser, Dirk Stippel, Roman-Ulrich Müller, Udo Holtick, Christoph Scheid, Martin Kann, Christine E. Kurschat and Franziska Grundmann
Microorganisms 2021, 9(8), 1666; https://doi.org/10.3390/microorganisms9081666 - 4 Aug 2021
Cited by 4 | Viewed by 3081
Abstract
The treatment options for cytomegalovirus (CMV) infections in immunosuppressed patients are limited, mainly consisting of (val-)ganciclovir (VGC/GCV) as the first-line treatment. We report on three transplant recipients, one stem cell transplant (allo-HSCT) patient and two kidney transplant (KTx) recipients, with prolonged CMV viremia [...] Read more.
The treatment options for cytomegalovirus (CMV) infections in immunosuppressed patients are limited, mainly consisting of (val-)ganciclovir (VGC/GCV) as the first-line treatment. We report on three transplant recipients, one stem cell transplant (allo-HSCT) patient and two kidney transplant (KTx) recipients, with prolonged CMV viremia treated with a combined therapy based on letermovir (LMV), CMV-specific intravenous immunoglobulins (IVIg), and VGC/GCV, which led to the sustained control of CMV viremia in all patients. Full article
(This article belongs to the Special Issue Molecular and Therapeutic Aspects of Viral Infections)
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