Viruses

23 pages, 4142 KiB

Open AccessArticle

In Silico Discovery and Evaluation of Inhibitors of the SARS−CoV−2 Spike Protein–HSPA8 Complex Towards Developing COVID-19 Therapeutic Drugs

by Liberty T. Navhaya, Thabe M. Matsebatlela, Mokgerwa Z. Monama and Xolani H. Makhoba

Viruses 2024, 16(11), 1726; https://doi.org/10.3390/v16111726 (registering DOI) - 31 Oct 2024

Abstract

The SARS−CoV−2 spike protein is pivotal in the COVID-19 virus’s life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually [...] Read more.

The SARS−CoV−2 spike protein is pivotal in the COVID-19 virus’s life cycle, facilitating viral attachment to host cells. It is believed that targeting this viral protein could be key to developing effective COVID-19 prophylactics. Using in silico techniques, this study sought to virtually screen for compounds from the literature that strongly bind and disrupt the stability of the HSPA8–spike protein complex. To evaluate the interactions between the individual proteins and the protein complex attained from protein–protein docking using BioLuminate, molecular docking was performed using the Maestro Schrodinger Suite. The screened small molecules met all bioavailability conditions, Lipinski’s and Veber’s rules, and the required medicinal chemistry properties. Protein–protein docking of the spike protein and HSPA8 identified the optimal pose with a PIPER cluster size of 65, a PIPER pose energy of –748.301 kcal/mol, and a PIPER pose score of –101.189 kcal/mol. Two small molecules, NSC36398 and NSC281245, showed promising docking scores against the spike protein individually and in a complex with HSPA8. NSC36398 had a docking score of –7.934 kcal/mol and a binding free energy of –39.52 kcal/mol with the viral spike protein and a docking score of –8.029 kcal/mol and binding free energy of –38.61 with the viral protein in complex with HSPA8, respectively. Mevastatin had a docking score of –5.099 kcal/mol and a binding free energy of –44.49 kcal/mol with the viral protein and a docking score of –5.285 kcal/mol and binding free energy of –36.65 kcal/mol with the viral protein in complex with HSPA8, respectively. These results, supported by extensive 2D interaction diagrams, suggest that NSC36398 and NSC281245 are potential drug candidates targeting SARS−CoV−2 spike protein. Full article

(This article belongs to the Special Issue Virology Research in South Africa—from a Great Legacy to an Optimistic Future)

14 pages, 9057 KiB

Open AccessArticle

Genome-Wide Analysis of p53 Targets Reveals SCN2A as a Novel Player in p53-Induced Cell Arrest in HPV-Positive Cells

by Yudi Zhang, Yi Liu, Xueyan Xing, Haibin Liu and Wuxiang Guan

Viruses 2024, 16(11), 1725; https://doi.org/10.3390/v16111725 - 31 Oct 2024

Abstract

The host transcription factor p53 is a critical tumor suppressor in HPV-induced carcinogenesis, regulating target genes involved in cell cycle arrest and apoptosis. However, the p53 targets have not been thoroughly analyzed in HPV-infected cells. In this study, p53 signaling in HPV16 and [...] Read more.

The host transcription factor p53 is a critical tumor suppressor in HPV-induced carcinogenesis, regulating target genes involved in cell cycle arrest and apoptosis. However, the p53 targets have not been thoroughly analyzed in HPV-infected cells. In this study, p53 signaling in HPV16 and HPV18 cells was activated by depleting the viral oncoprotein E6. Subsequently, p53-regulated genes were identified by comparing them with genes altered in p53-silenced cells. True p53 targets were defined as genes with at least one overlapping p53 binding site and ChIP peak near their locus. Our analysis revealed that while some p53 targets were common to both the HPV16 and HPV18 cells, the majority of the targets differed between these two types, potentially contributing to the varying prevalence of HPV16 and HPV18 in cervical cancer. Additionally, we identified SCN2A as a novel p53 target involved in p53-induced cell cycle arrest in HPV-related carcinogenesis. This study provides new insights into the mechanisms by which p53 inhibits HPV-induced carcinogenesis. Full article

(This article belongs to the Section General Virology)

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11 pages, 254 KiB

Open AccessArticle

Effectiveness of Direct Antiviral Agents in People with HCV-Monoinfection Compared to HCV/HIV Coinfection in a Real Life Setting

by Cristina Guadalupe Román López, Salma Triana González, Ana Luz Cano Díaz, Dulce Daniela Flores Lopez, José Antonio Mata Marín and Jesús Enrique Gaytán Martínez

Viruses 2024, 16(11), 1724; https://doi.org/10.3390/v16111724 - 31 Oct 2024

Abstract

Direct-acting antivirals (DAA) are effective in patients with hepatitis C virus (HCV) infection, but there is little information about real-world effectiveness in people living with human immunodeficiency virus (PLH). The aim of this study was to determinate the effectiveness of DAA to achieve [...] Read more.

Direct-acting antivirals (DAA) are effective in patients with hepatitis C virus (HCV) infection, but there is little information about real-world effectiveness in people living with human immunodeficiency virus (PLH). The aim of this study was to determinate the effectiveness of DAA to achieve sustained virologic response at week 12 post-treatment (SVR12) in PLH with HCV coinfection and in people with HCV-monoinfection. We conducted a prospective cohort. The full analysis set (FAS) included all subjects enrolled in the study; the modified analysis set (MAS) excluded cases with missing data to evaluate SVR12. A total of 278 people were included, 130 (46.7%) with HCV/HIV-coinfection and 148 (53.2%) with HCV-monoinfection. In the HCV/HIV-coinfection group, 82 (63%) received GLE/PIB for 8 weeks, 45 (34.6%) received SOF/VEL for 12 weeks, and 3 (2.3%) were treated with SOF/VEL + RBV for 12 weeks. In the HCV-monoinfection group, 62 (41.8%) received GLE/PIB for 8 weeks, 28 (18.9%) received SOF/VEL for 12 weeks, and 58 (39.1%) participants were treated with SOF/VEL + RBV for 12 weeks. In the FAS analysis, SVR12 was 81.6% in the HCV/HIV-coinfection group and 86.4% in the HCV-monoinfection group (p = 0.128). In the MAS analysis, both groups achieved 100% of SVR12. In this cohort, the effectiveness of DAA to achieve SVR12 was similar between HCV/HIV-coinfection and HCV-monoinfection cases, regardless of advanced liver disease with no differences between treatment regimens. Full article

(This article belongs to the Special Issue Viral Hepatitis in Latin America and the Caribbean)

15 pages, 1211 KiB

Open AccessReview

Prevalence, Risk Factors, and Clinical Profiles of Hepatitis D Virus in Nigeria: A Systematic Review, 2009–2024

by Victor Abiola Adepoju, Donald Chinazor Udah and Qorinah Estiningtyas Sakilah Adnani

Viruses 2024, 16(11), 1723; https://doi.org/10.3390/v16111723 - 31 Oct 2024

Abstract

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic [...] Read more.

Background: The World Health Organization (WHO) recommends hepatitis D virus (HDV) screening among hepatitis B virus (HBV) infected individuals, with a focus on priority populations in resource-limited settings like Nigeria. HDV infection is a growing public health challenge, particularly among individuals with chronic hepatitis B virus (HBV) infection. HDV accelerates liver disease progression and significantly increases the risk of cirrhosis and hepatocellular carcinoma. Despite this, the epidemiology of HDV in Nigeria remains inadequately documented. This scoping review critically evaluates the prevalence, risk factors, and clinical outcomes of HDV co-infection among HBV patients in Nigeria. Method: We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. The review included observational cross-sectional studies published between 2009 and 2024. We focused on studies that used Immunoglobulin G (IgG) antibody testing or RNA-based diagnostics to assess HDV prevalence. We included PubMed, Google Scholar, and Dimensions databases due to their broad indexing and coverage of peer-reviewed articles and accessibility. We screened the studies for their relevance to HDV prevalence, risk factors, and clinical outcomes, while excluding those that only tested for IgM or HDV antigen. Eleven studies, with a combined sample size of 2308 participants, were included in the final analysis. We performed a narrative synthesis of the findings, considering geographic, gender, and age-based variations in HDV prevalence and clinical impact. Results: HDV prevalence among HBV-infected individuals in Nigeria ranged from 2.0% to 31.6%. The highest prevalence was reported in the Southwest (31.6%) among malaria patients, while lower rates were observed in the Southeast (2.8%). Prevalence was higher in males, particularly those aged 21–30 years in the Southwest and 31–40 years in other regions. RNA-based testing provided more accurate data on active viremia, with viremic HDV prevalence rates ranging from 3.2% to 16%. Triple infection with HIV/HBV/HDV was associated with significantly lower CD4+ cell counts and worse clinical outcomes, including elevated liver enzymes and rapid progression to liver cancer. Key risk factors for HDV co-infection included multiple sexual partners, sharing of needles, and unsafe medical practices. Co-infected patients demonstrated worse clinical outcomes, such as elevated liver enzymes, decompensated cirrhosis, and higher rates of hepatocellular carcinoma. Conclusions: Our review underscores the urgent need for routine HDV screening among HBV patients in Nigeria, especially given the severe clinical consequences of co-infection. The recent WHO guidelines recommending HDV screening align with our findings, which emphasize the importance of RNA-based HDV testing among HBV-positive patients to improve diagnostic accuracy. Public health efforts should prioritize tailored interventions based on geographic, age, and gender disparities in HDV prevalence. Triple infection with HIV/HBV/HDV requires integrated care models to address both immune suppressions as indicated by diminished CD4 cell count and liver disease progression, as these patients face worse outcomes. Targeted HDV screening in mostly affected demographics and geographies and improved Nigeria capacity for cheaper HDV RNA/PCR diagnostics can reduce liver-related morbidity and mortality caused by HBV, which can be worsened and accelerated by HDV coinfection. Full article

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

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27 pages, 3550 KiB

Open AccessReview

Cottontail Rabbit Papillomavirus (CRPV) Related Animal Models for Head and Neck Cancer Research: A Comprehensive Review of the Literature

by Michael Bette and Robert Mandic

Viruses 2024, 16(11), 1722; https://doi.org/10.3390/v16111722 - 31 Oct 2024

Abstract

Having suitable animal models is crucial to mimic human disease states and for the successful transfer of experimental data into clinical practice. In the field of papillomavirus research, the domestic rabbit (Oryctolagus cuniculus) has served as an indispensable model organism for [...] Read more.

Having suitable animal models is crucial to mimic human disease states and for the successful transfer of experimental data into clinical practice. In the field of papillomavirus research, the domestic rabbit (Oryctolagus cuniculus) has served as an indispensable model organism for almost 100 years. The identification and characterization of the first papillomaviruses in rabbits, their carcinogenic potential and their immunogenicity have contributed significantly to the state of knowledge on the genetics and life cycle of papillomaviruses in general, as well as the development of antiviral strategies such as vaccination procedures. Due to the high species specificity of papillomaviruses, only rabbit papillomaviruses (RPVs) can be used for animal studies on papilloma-based tumor diseases in the rabbit. The major focus of this article is on cottontail rabbit papillomavirus (CRPV)-related rabbit squamous cell carcinoma (RSCC). A brief history outlines the discovery and generation of experimentally used RSCC tumors. A comprehensive overview of the current CRPV-associated VX2 carcinoma-based tumor models with a major focus on human head and neck squamous cell carcinoma (HNSCC) tumor models is provided, and their strengths in terms of transferability to human HNSCC are discussed. Full article

(This article belongs to the Special Issue Animal Papillomaviruses Research)

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9 pages, 529 KiB

Open AccessArticle

Prolonged Visual Evoked Potential Latencies in Dogs Naturally Infected with Canine Distemper Virus

by Mary Gutiérrez, Luis Delucchi, Alejandro Bielli and José Manuel Verdes

Viruses 2024, 16(11), 1721; https://doi.org/10.3390/v16111721 - 31 Oct 2024

Abstract

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to [...] Read more.

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to similar clinical presentation and pathophysiological mechanisms. In MS, visual evoked potentials (VEPs) have been identified as a reliable marker for disease progression, enabling the early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results in the CDV-infected group revealed a bilateral increase in the latency of N1, P1, N2, P2, and N3 waves of the VEPs, without any alterations in their amplitudes. No significant differences were observed in the ERG between the groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neurological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease. Full article

(This article belongs to the Special Issue Canine Distemper Virus)

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14 pages, 2658 KiB

Open AccessArticle

Droplet Digital PCR Enhances Sensitivity of Canine Distemper Virus Detection

by Victoria Iribarnegaray, Guillermo Godiño, Camila Larrañaga, Kanji Yamasaki, José Manuel Verdes and Rodrigo Puentes

Viruses 2024, 16(11), 1720; https://doi.org/10.3390/v16111720 - 31 Oct 2024

Abstract

Canine distemper virus (CDV) poses a substantial threat to diverse carnivorans, leading to systemic and often fatal diseases. Accurate and prompt diagnosis is paramount for effective management and curbing further transmission. This study evaluates the diagnostic performance of droplet digital PCR (ddPCR) in [...] Read more.

Canine distemper virus (CDV) poses a substantial threat to diverse carnivorans, leading to systemic and often fatal diseases. Accurate and prompt diagnosis is paramount for effective management and curbing further transmission. This study evaluates the diagnostic performance of droplet digital PCR (ddPCR) in comparison to conventional reverse-transcription (RT-PCR) and quantitative reverse-transcription real-time PCR (RT-qPCR). Seventy-six clinical samples were collected from dogs with CDV symptoms diagnosed by specialized veterinarians, and sixteen samples from apparently healthy individuals. Conventional PCR, quantitative real-time PCR, and ddPCR were deployed, and their diagnostic capabilities were meticulously assessed. DdPCR exhibited heightened analytical sensitivity, reaching a detection limit of 3 copies/μL, whereas RT-qPCR had a detection limit of 86 copies/μL. The comparative analysis between clinical diagnosis and molecular techniques, including RT-PCR and RT-qPCR, demonstrated low concordance, with Kappa coefficients of 0.268 and 0.324, respectively. In contrast, ddPCR showed a moderate concordance, with a Kappa coefficient of 0.477. The sensitivity was 42.4% for RT-PCR, 57.9% for RT-qPCR, and 72.4% for ddPCR, with 100% specificity for all methods. This study underscores ddPCR’s superior sensitivity and agreement with clinical CDV diagnosis, even at low viral concentrations, suggesting it as a promising alternative for CDV diagnosis. Full article

(This article belongs to the Special Issue Canine Distemper Virus)

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15 pages, 9374 KiB

Open AccessArticle

Pathological Study of Demyelination with Cellular Reactions in the Cerebellum of Dogs Infected with Canine Distemper Virus

by José Manuel Verdes, Camila Larrañaga, Guillermo Godiño, Belén Varela, Victoria Yozzi, Victoria Iribarnegaray, Luis Delucchi and Kanji Yamasaki

Viruses 2024, 16(11), 1719; https://doi.org/10.3390/v16111719 - 31 Oct 2024

Abstract

The purpose of this study was to examine the relationship between demyelination and cellular reactions in the cerebellum of Canine Distemper Virus (CDV)-infected dogs. We subdivided the disease staging by adding the degree of demyelination determined by Luxol Fast Blue staining to the [...] Read more.

The purpose of this study was to examine the relationship between demyelination and cellular reactions in the cerebellum of Canine Distemper Virus (CDV)-infected dogs. We subdivided the disease staging by adding the degree of demyelination determined by Luxol Fast Blue staining to the previously reported disease staging from the acute stage to the chronic stage, and investigated the relationship between demyelination in the cerebellum and the number and histological changes in astroglia, microglia, and Purkinje cells in each stage. Reactions of astrocytes and microglia were observed at an early stage when demyelination was not evident. Changes progressed with demyelination. Demyelination initially began in the medulla adjoining the fourth ventricle and gradually spread to the entire cerebellum, including the lobes. CDV immune-positive granules were seen from the early stage, and inclusion bodies also appeared at the same time. CDV immune-positive reaction and inclusion bodies were observed in astrocytes, microglia, neurons, ependymal cells, and even leptomeningeal mononuclear cells. On the other hand, infiltration of CDV-immunoreactive particles from the pia mater to the gray matter and further into the white matter through the granular layer was observed from an early stage. Purkinje cells decreased from the intermediate stage, and a decrease in cells in the granular layer was also observed. There was no clear association between age and each stage, and the stages did not progress with age. Full article

(This article belongs to the Special Issue Canine Distemper Virus)

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13 pages, 723 KiB

Open AccessArticle

Expression of Toll-like Receptor Genes and Antiviral Cytokines in Macrophage-like Cells in Response to Indole-3-carboxylic Acid Derivative

by Alexander Narovlyansky, Alexander Pronin, Vladislav Poloskov, Alexander Sanin, Marina Mezentseva, Irina Fedyakina, Irina Suetina, Igor Zubashev, Felix Ershov, Marina Filimonova, Valentina Surinova, Irina Volkova and Egor Bogdanov

Viruses 2024, 16(11), 1718; https://doi.org/10.3390/v16111718 - 31 Oct 2024

Abstract

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. [...] Read more.

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the TLR3 and TLR4 genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (IFNA1, IFNA2, IFNB1, IFNK, and IFNλ1) genes with simultaneous stimulation of the expression of interferon receptor (IFNAR1 and IFNAR2) genes and signalling molecule (JAK1 and ISG15) genes was detected. Increased fold stimulation of the expression of the cytokine genes IL6, TNFA, IL12A, and IL12B was also observed. Thus, it is shown that the XXV is an activator of TLR genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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31 pages, 5365 KiB

Open AccessArticle

Increased Susceptibility of Rousettus aegyptiacus Bats to Respiratory SARS-CoV-2 Challenge Despite Its Distinct Tropism for Gut Epithelia in Bats

by Björn-Patrick Mohl, Claudia Blaurock, Angele Breithaupt, Alexander Riek, John R. Speakman, Catherine Hambly, Marcel Bokelmann, Gang Pei, Balal Sadeghi, Anca Dorhoi and Anne Balkema-Buschmann

Viruses 2024, 16(11), 1717; https://doi.org/10.3390/v16111717 - 31 Oct 2024

Abstract

Increasing evidence suggests bats are the ancestral hosts of the majority of coronaviruses. In general, coronaviruses primarily target the gastrointestinal system, while some strains, especially Betacoronaviruses with the most relevant representatives SARS-CoV, MERS-CoV, and SARS-CoV-2, also cause severe respiratory disease in humans and [...] Read more.

Increasing evidence suggests bats are the ancestral hosts of the majority of coronaviruses. In general, coronaviruses primarily target the gastrointestinal system, while some strains, especially Betacoronaviruses with the most relevant representatives SARS-CoV, MERS-CoV, and SARS-CoV-2, also cause severe respiratory disease in humans and other mammals. We previously reported the susceptibility of Rousettus aegyptiacus (Egyptian fruit bats) to intranasal SARS-CoV-2 infection. Here, we compared their permissiveness to an oral infection versus respiratory challenge (intranasal or orotracheal) by assessing virus shedding, host immune responses, tissue-specific pathology, and physiological parameters. While respiratory challenge with a moderate infection dose of 1 × 10⁴ TCID₅₀ caused a systemic infection with oral and nasal shedding of replication-competent virus, the oral challenge only induced nasal shedding of low levels of viral RNA. Even after a challenge with a higher infection dose of 1 × 10⁶ TCID₅₀, no replication-competent virus was detectable in any of the samples of the orally challenged bats. We postulate that SARS-CoV-2 is inactivated by HCl and digested by pepsin in the stomach of R. aegyptiacus, thereby decreasing the efficiency of an oral infection. Therefore, fecal shedding of RNA seems to depend on systemic dissemination upon respiratory infection. These findings may influence our general understanding of the pathophysiology of coronavirus infections in bats. Full article

(This article belongs to the Special Issue Antiviral Immune Responses of Bat)

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14 pages, 3221 KiB

Open AccessArticle

Current Trends in HIV Infection in the Republic of Crimea

by Aleksei Mazus, Anastasiia Antonova, Ruslan Adgamov, Daria Ogarkova, Anna Kuznetsova, Andrei Pochtovyi, Elena Tsyganova, Vladimir Zlobin, Vladimir Gushchin, Andrei Plutnitskii and Aleksandr Gintsburg

Viruses 2024, 16(11), 1716; https://doi.org/10.3390/v16111716 - 31 Oct 2024

Abstract

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a [...] Read more.

The aim of this study was to analyse the trends in HIV infection, including diagnostic ones, in the Republic of Crimea in the period of 2014–2023. The source of data for this study was various statistical forms and reports. The findings revealed a significant downward trend in HIV incidence and a significant upward trend in HIV prevalence. The mortality rate was stable. The coverage of HIV testing and antiretroviral therapy increased over time. The number of patients with a suppressed viral load in the Republic fluctuated in different years of observation and reached 81% in 2023. In the second part of this study, we analysed the demographic and clinical laboratory characteristics of newly diagnosed patients with HIV. A predominance of men was noted. The proportion of injection drug users (IDUs) decreased, and the proportion of new HIV infection cases through heterosexual contacts increased. An increase in the median age of patients was also noted. Analysis of CD4 cell counts revealed significant differences between subgroups by gender, age, and route of infection. The longest time to disease detection was typical for IDUs. A comprehensive assessment of HIV infection trends in Crimea allows us to evaluate the effectiveness of measures and decisions taken on the issue of HIV infection. Full article

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

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11 pages, 250 KiB

Open AccessArticle

Spectrum of Non-Nucleoside Reverse Transcriptase Inhibitor-Associated Drug Resistance Mutations in Persons Living with HIV-1 Receiving Rilpivirine

by Pavithra Nagarajan, Jinru Zhou, Giulia Di Teodoro, Francesca Incardona, Carole Seguin-Devaux, Rolf Kaiser, Ana B. Abecasis, Perpetua Gomes, Kaiming Tao, Maurizio Zazzi and Robert W. Shafer

Viruses 2024, 16(11), 1715; https://doi.org/10.3390/v16111715 - 31 Oct 2024

Abstract

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV). Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in [...] Read more.

Introduction: Few data are currently available on the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTI) resistance mutations selected in persons living with HIV-1 (PLWH) who develop virological failure while receiving rilpivirine (RPV). Methods: We analyzed pooled HIV-1 RT genotypic data from 280 PLWH in the multicenter EuResist database and 115 PLWH in the Stanford HIV Drug Resistance Database (HIVDB) who received RPV as their only NNRTI. Results: Among the 395 PLWH receiving RPV, 180 (45.6%) had one or more NNRTI-associated DRMs. Overall, 44 NNRTI-associated DRMs were identified, including 26 that occurred in two or more PLWHs. Seven mutations had a prevalence ≥10% among the 180 PLWH with one or more NNRTI-associated DRM: E138K (32.2%), V90I (25.0%), K101E (17.8%), Y181C (17.2%), E138A (13.9%), H221Y (12.2%), and K103N (10.6%). Y181C was significantly more likely to co-occur with K101E, V179F, H221Y, and M230L. Ten novel non-polymorphic mutations at known NNRTI-associated mutation positions were also identified, usually in just one PLWH: L100F, V108A, T139I, P225S, M230V, Y232C, and T240A/I/M/S. Conclusions: Our analysis extends the spectrum of mutations emerging in PLWH receiving RPV. Additional phenotypic characterization of RPV-selected mutations is necessary to better understand their biological and possible clinical significance. Full article

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

21 pages, 1299 KiB

Open AccessReview

The Effects of Viral Structural Proteins on Acidic Phospholipids in Host Membranes

by Ricardo de Souza Cardoso and Akira Ono

Viruses 2024, 16(11), 1714; https://doi.org/10.3390/v16111714 - 31 Oct 2024

Abstract

Enveloped viruses rely on host membranes for trafficking and assembly. A substantial body of literature published over the years supports the involvement of cellular membrane lipids in the enveloped virus assembly processes. In particular, the knowledge regarding the relationship between viral structural proteins [...] Read more.

Enveloped viruses rely on host membranes for trafficking and assembly. A substantial body of literature published over the years supports the involvement of cellular membrane lipids in the enveloped virus assembly processes. In particular, the knowledge regarding the relationship between viral structural proteins and acidic phospholipids has been steadily increasing in recent years. In this review, we will briefly review the cellular functions of plasma membrane-associated acidic phospholipids and the mechanisms that regulate their local distribution within this membrane. We will then explore the interplay between viruses and the plasma membrane acidic phospholipids in the context of the assembly process for two enveloped viruses, the influenza A virus (IAV) and the human immunodeficiency virus type 1 (HIV-1). Among the proteins encoded by these viruses, three viral structural proteins, IAV hemagglutinin (HA), IAV matrix protein-1 (M1), and HIV-1 Gag protein, are known to interact with acidic phospholipids, phosphatidylserine and/or phosphatidylinositol (4,5)-bisphosphate. These interactions regulate the localization of the viral proteins to and/or within the plasma membrane and likely facilitate the clustering of the proteins. On the other hand, these viral proteins, via their ability to multimerize, can also alter the distribution of the lipids and may induce acidic-lipid-enriched membrane domains. We will discuss the potential significance of these interactions in the virus assembly process and the property of the progeny virions. Finally, we will outline key outstanding questions that need to be answered for a better understanding of the relationships between enveloped virus assembly and acidic phospholipids. Full article

(This article belongs to the Special Issue Host Membranes and Virus Infection Cycle)

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10 pages, 1043 KiB

Open AccessArticle

A Sensitivity and Consistency Comparison Between Next-Generation Sequencing and Sanger Sequencing in HIV-1 Pretreatment Drug Resistance Testing

by Ying Zhou, Fei Ouyang, Xiaoyan Liu, Jing Lu, Haiyang Hu, Qi Sun and Haitao Yang

Viruses 2024, 16(11), 1713; https://doi.org/10.3390/v16111713 - 31 Oct 2024

Abstract

Next-generation sequencing (NGS) for HIV drug resistance (DR) testing has an increasing number of applications for the detection of low-abundance drug-resistant variants (LA-DRVs) in regard to its features as a quasi-species. However, there is less information on its detection performance in DR detection [...] Read more.

Next-generation sequencing (NGS) for HIV drug resistance (DR) testing has an increasing number of applications for the detection of low-abundance drug-resistant variants (LA-DRVs) in regard to its features as a quasi-species. However, there is less information on its detection performance in DR detection with NGS. To determine the feasibility of using NGS technology in LA-DRV detection for HIV-1 pretreatment drug resistance, 80 HIV-infected individuals who had never undergone antiretroviral therapy were subjected to both NGS and Sanger sequencing (SS) in HIV-1 drug resistance testing. The results reported in this study show that NGS exhibits higher sensitivity for drug resistance identification than SS at a 5% detection threshold. NGS showed a better consistency compared with that of SS for both protease inhibitors (PIs) and integrase inhibitors (INSTIs), with a figure amounting to more than 90%, but worse consistency in nucleotide reverse transcriptase inhibitors (NRTIs), with a consistency ranging from only 61.25% to 87.50%. The consistency of non-nucleotide reverse transcriptase inhibitors (NNRTIs) between NGS and SS was around 85%. NGS showed the highest sensitivity of 87.0% at a 5% threshold. The application of NGS technology in HIV-1 genotype resistance detection in different populations infected with HIV requires further documentation and validation. Full article

(This article belongs to the Special Issue Next Generation Sequencing for HIV Drug Resistance Testing, 2nd Edition)

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14 pages, 6160 KiB

Open AccessArticle

RNA-Seq Reveals Transcriptome Changes Following Zika Virus Infection in Fetal Brains in c-Flip Knockdown Mice

by Ting Xie, Qiqi Chen, Nina Li, Shengze Zhang, Lin Zhu, Shaohui Bai, Haolu Zha, Weijian Tian, Chuming Luo, Nan Wu, Xuan Zou, Shisong Fang, Yuelong Shu, Jianhui Yuan, Ying Jiang and Huanle Luo

Viruses 2024, 16(11), 1712; https://doi.org/10.3390/v16111712 - 31 Oct 2024

Abstract

The FADD-like interleukin-1β converting enzyme (FLICE)-inhibitory protein (c-FLIP) plays a crucial role in various biological processes, including apoptosis and inflammation. However, the complete transcriptional profile altered by the c-FLIP is not fully understood. Furthermore, the impact of the c-FLIP deficiency on the transcriptome [...] Read more.

The FADD-like interleukin-1β converting enzyme (FLICE)-inhibitory protein (c-FLIP) plays a crucial role in various biological processes, including apoptosis and inflammation. However, the complete transcriptional profile altered by the c-FLIP is not fully understood. Furthermore, the impact of the c-FLIP deficiency on the transcriptome during a Zika virus (ZIKV) infection, which induces apoptosis and inflammation in the central nervous system (CNS), has not yet been elucidated. In this study, we compared transcriptome profiles between wild-type (WT) and the c-Flip heterozygous knockout mice (c-Flip^+/−) fetal heads at embryonic day 13.5 from control and PBS-infected WT dams mated with c-Flip^+/− sires. In the non-infected group, we observed differentially expressed genes (DEGs) mainly involved in embryonic development and neuron development. However, the ZIKV infection significantly altered the transcriptional profile between WT and the c-Flip^+/− fetal heads. DEGs in pattern recognition receptor (PRR)-related signaling pathways, such as the RIG-I-like receptor signaling pathway and Toll-like receptor signaling pathway, were enriched. Moreover, the DEGs were also enriched in T cells, indicating that the c-FLIP participates in both innate and adaptive immune responses upon viral infection. Furthermore, our observations indicate that DEGs are associated with sensory organ development and eye development, suggesting a potential role for the c-FLIP in ZIKV-induced organ development defects. Overall, we have provided a comprehensive transcriptional profile for the c-FLIP and its modulation during a ZIKV infection. Full article

(This article belongs to the Special Issue Innate Immunity to Virus Infection 2nd Edition)

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18 pages, 3661 KiB

Open AccessArticle

Isolation and Characterization of a Bacteriophage with Potential for the Control of Multidrug-Resistant Salmonella Strains Encoding Virulence Factors Associated with the Promotion of Precancerous Lesions

by Luis Amarillas, Fedra Padilla-Lafarga, Rubén Gerardo León Chan, Jorge Padilla, Yadira Lugo-Melchor, Jesús Enrique López Avendaño, Luis Lightbourn-Rojas and Mitzi Estrada-Acosta

Viruses 2024, 16(11), 1711; https://doi.org/10.3390/v16111711 - 31 Oct 2024

Abstract

Background: Antimicrobial-resistant bacteria represent a serious threat to public health. Among these bacteria, Salmonella is of high priority because of its morbidity levels and its ability to induce different types of cancer. Aim: This study aimed to identify Salmonella strains encoding genes linked [...] Read more.

Background: Antimicrobial-resistant bacteria represent a serious threat to public health. Among these bacteria, Salmonella is of high priority because of its morbidity levels and its ability to induce different types of cancer. Aim: This study aimed to identify Salmonella strains encoding genes linked to the promotion of precancerous lesions and to isolate a bacteriophage to evaluate its preclinical potential against these bacteria. Methodology: An epidemiological approach based on wastewater analysis was employed to isolate Salmonella strains and detect genes associated with the induction of precancerous lesions. Antimicrobial susceptibility was assessed by the disk diffusion method. A bacteriophage was isolated via the double agar technique, and its morphological characteristics, stability, host range, replication dynamics, and ability to control Salmonella under different conditions were evaluated. The bacteriophage genome was sequenced and analyzed using bioinformatics tools. Results: Thirty-seven Salmonella strains were isolated, seventeen of which contained the five genes associated with precancerous lesions’ induction. These strains exhibited resistance to multiple antimicrobials, including fluoroquinolones. A bacteriophage from the Autographiviridae family with lytic activity against 21 bacterial strains was isolated. This phage exhibited a 20 min replication cycle, releasing 52 ± 3 virions per infected cell. It demonstrated stability and efficacy in reducing the Salmonella concentration in simulated gastrointestinal conditions, and its genome lacked genes that represent a biosafety risk. Conclusion: This bacteriophage shows promising preclinical potential as a biotherapeutic agent against Salmonella. Full article

(This article belongs to the Section Bacterial Viruses)

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17 pages, 1387 KiB

Open AccessReview

Evaluation of Interfering RNA Efficacy in Treating Hepatitis B: Is It Promising?

by Giovana Paula Angelice, Pedro Henrique Roque, Gabriel Valente, Krishna Galvão, Livia Melo Villar, Vinicius Motta Mello, Francisco C. A. Mello and Bárbara Vieira Lago

Viruses 2024, 16(11), 1710; https://doi.org/10.3390/v16111710 - 31 Oct 2024

Abstract

Background: Despite an existing safe and effective vaccine for hepatitis B virus (HBV), it is still a major public health concern. Nowadays, several drugs are used to treat chronic hepatitis B; however, full healing remains controversial. The viral covalently closed circular DNA (cccDNA) [...] Read more.

Background: Despite an existing safe and effective vaccine for hepatitis B virus (HBV), it is still a major public health concern. Nowadays, several drugs are used to treat chronic hepatitis B; however, full healing remains controversial. The viral covalently closed circular DNA (cccDNA) formed by HBV forms a major challenge in its treatment, as does the ability of HBV to integrate itself into the host genome, which enables infection reactivation. Interfering RNA (RNAi) is a gene-silencing post-transcriptional mechanism which forms as a promising alternative to treat chronic hepatitis B. The aim of the present review is to assess the evolution of hepatitis B treatment approaches based on using RNA interference. Methods: Data published between 2016 and 2023 in scientific databases (PubMed, PMC, LILACS, and Bireme) were assessed. Results: In total, 76,949 articles were initially identified and quality-checked, and 226 eligible reports were analyzed in depth. The main genomic targets, delivery systems, and major HBV therapy innovations are discussed in this review. This review reinforces the therapeutic potential of RNAi and identifies the need for conducting further studies to fill the remaining gaps between bench and clinical practice. Full article

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

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18 pages, 1390 KiB

Open AccessReview

Rice Yellow Mottle Virus (RYMV): A Review

by Linda Appianimaa Abrokwah, Stephen Kwame Torkpo, Guilherme da Silva Pereira, Allen Oppong, John Eleblu, Justin Pita and Samuel Kwame Offei

Viruses 2024, 16(11), 1707; https://doi.org/10.3390/v16111707 - 31 Oct 2024

Abstract

Rice (Oryza spp.) is mostly grown directly from seed and sown on wet or dry seed beds or usually used as transplants on nursery beds. Among all the economically important viral diseases in the world, rice yellow mottle virus (RYMV) is only [...] Read more.

Rice (Oryza spp.) is mostly grown directly from seed and sown on wet or dry seed beds or usually used as transplants on nursery beds. Among all the economically important viral diseases in the world, rice yellow mottle virus (RYMV) is only prevalent in rice-growing countries in Africa. RYMV has become the main rice production constraint in Africa over the last 20–25 years, causing yield losses of 10 to 100% depending on the age of the plant at the time of infection, degree of varietal susceptibility and the existing climatic conditions. Good agricultural practices and biotechnological tools in the development of improved resistant cultivars have been extensively utilized in controlling the disease. This review focuses on RYMV, its epidemiology, serological and molecular typing, disease management and the way forward for sustainable rice production. Full article

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

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15 pages, 3606 KiB

Open AccessArticle

Surfactant Protein A Inhibits Human Rhinovirus C Binding and Infection of Airway Epithelial Cells from Pediatric Asthma

by Sasipa Tanyaratsrisakul, Yury A. Bochkov, Vanessa White, Heejung Lee, Jessica Loeffler, Jamie Everman, Allison M. Schiltz, Kristy L. Freeman, Katharine L. Hamlington, Elizabeth A. Secor, Nathan D. Jackson, Hong Wei Chu, Andrew H. Liu, Julie G. Ledford, Monica Kraft, Max A. Seibold, Dennis R. Voelker and Mari Numata

Viruses 2024, 16(11), 1709; https://doi.org/10.3390/v16111709 - 30 Oct 2024

Abstract

Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. Surfactant protein A (SP-A) plays a critical role in regulating pulmonary innate immunity by binding to numerous [...] Read more.

Rhinovirus C (RV-C) infection can trigger asthma exacerbations in children and adults, and RV-C-induced wheezing illnesses in preschool children correlate with the development of childhood asthma. Surfactant protein A (SP-A) plays a critical role in regulating pulmonary innate immunity by binding to numerous respiratory pathogens. Mature SP-A consists of multiple isoforms that form the hetero-oligomers of SP-A1 and SP-A2, organized in 18-mers. In this report, we examined the efficacy of SP-A to antagonize RV-C infection using the wild-type (RV-C15) and reporter-expressing (RV-C15-GFP) viruses in differentiated nasal epithelial cells (NECs) from asthmatic and non-asthmatic children. We also determined the antiviral mechanism of action of SP-A on RV-C15 infection. The native SP-A was purified from alveolar proteinosis patients. The recombinant (r) SP-A1 and SP-A2 variants were expressed in FreeStyle™ 293-F cells. SP-A reduced the fluorescent focus-forming units (FFUs) after RV-C15-GFP infection of NECs by 99%. Both simultaneous and 4 h post-infection treatment with SP-A inhibited RV-C15 and RV-C15-GFP viral RNA load by 97%. In addition, the antiviral genes and chemokines (IFN-λ, IRF-7, MDA-5, and CXLC11) were not induced in the infected NECs due to the inhibition of RV-C propagation by SP-A. Furthermore, SP-A bound strongly to RV-C15 in a dose- and Ca²⁺-dependent manner, and this interaction inhibited RV-C15 binding to NECs. In contrast, rSP-A1 did not bind to solid-phase RV-C15, whereas the rSP-A2 variants, [A₉₁, K₂₂₃] and [P₉₁, Q₂₂₃], had strong binding affinities to RV-C15, similar to native SP-A. This study demonstrates that SP-A might have potential as an antiviral for RV infection and RV-induced asthma exacerbations. Full article

(This article belongs to the Special Issue Rhinoviruses and Asthma)

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