Viruses

26 pages, 5334 KiB

Open AccessArticle

Phage vB_KlebPS_265 Active Against Resistant/MDR and Hypermucoid K2 Strains of Klebsiella pneumoniae

by Vyacheslav I. Yakubovskij, Vera V. Morozova, Yuliya N. Kozlova, Artem Yu. Tikunov, Valeria A. Fedorets, Elena V. Zhirakovskaya, Igor V. Babkin, Alevtina V. Bardasheva and Nina V. Tikunova

Viruses 2025, 17(1), 83; https://doi.org/10.3390/v17010083 - 9 Jan 2025

Abstract

Klebsiella pneumoniae is an important opportunistic pathogen often resistant to antibiotics. Specific phages can be useful in eliminating infection caused by K. pneumoniae. Klebsiella phage vB_KlebPS_265 (KlebP_265) and its host strain were isolated from the sputum of a patient with Klebsiella infection. [...] Read more.

Klebsiella pneumoniae is an important opportunistic pathogen often resistant to antibiotics. Specific phages can be useful in eliminating infection caused by K. pneumoniae. Klebsiella phage vB_KlebPS_265 (KlebP_265) and its host strain were isolated from the sputum of a patient with Klebsiella infection. KlebP_265 was specific mainly to K. pneumoniae-type K2 strains including hypermucoid strains. Most of the hypermucoid KlebP_265-susceptible strains were antibiotic-resistant. This siphophage demonstrated good lytic activity and stability. The KlebP_265 genome was 46,962 bp and contained 88 putative genes; functions were predicted for 37 of them. No genes encoding integrases, toxins, or antibiotic resistance were found in the genome. So, KlebP_265 could potentially be a therapeutic phage. Comparative analysis indicated that KlebP_265 with the most relative Klebsiella phage DP01 formed the putative Dipiunovirus genus. Genome analysis revealed a large monophyletic group of phages related to KlebP_265 and DP01. This group is divided into two monophyletic clusters of phages forming new putative subfamilies Skatevirinae and Roufvirinae. Phylogenetic analysis showed extensive gene exchange between phages from the putative subfamilies. Horizontal transfer even involved conservative genes and led to clear genomic mosaicism, indicating multiple recombination events in the ancestral phages during evolution. Full article

(This article belongs to the Section Bacterial Viruses)

13 pages, 4189 KiB

Open AccessArticle

Monovalent Lectin Microvirin Utilizes Hydropathic Recognition of HIV-1 Env for Inhibition of Virus Cell Infection

by Bibek Parajuli, Kriti Acharya, Harry Charles Bach, Shiyu Zhang, Cameron F. Abrams and Irwin Chaiken

Viruses 2025, 17(1), 82; https://doi.org/10.3390/v17010082 - 9 Jan 2025

Abstract

Microvirin is a lectin molecule known to have monovalent interaction with glycoprotein gp120. A previously reported high-resolution structural analysis defines the mannobiose-binding cavity of Microvirin. Nonetheless, structure does not directly define the energetics of binding contributions of protein contact residues. To better understand [...] Read more.

Microvirin is a lectin molecule known to have monovalent interaction with glycoprotein gp120. A previously reported high-resolution structural analysis defines the mannobiose-binding cavity of Microvirin. Nonetheless, structure does not directly define the energetics of binding contributions of protein contact residues. To better understand the nature of the MVN-Env glycan interaction, we used mutagenesis to evaluate the residue contributions to the mannobiose binding site of MVN that are important for Env gp120 glycan binding. MVN binding site amino acid residues were individually replaced by alanine, and the resulting purified recombinant MVN variants were examined for gp120 interaction using competition Enzyme-Linked Immunosorbent Assay (ELISA), biosensor surface plasmon resonance, calorimetry, and virus neutralization assays. Our findings highlight the role of both uncharged polar and non-polar residues in forming a hydropathic recognition site for the monovalent glycan engagement of Microvirin, in marked contrast to the charged residues utilized in the two Cyanovirin-N (CVN) glycan-binding sites. Full article

(This article belongs to the Special Issue Role of Lectins in Viral Infections and Antiviral Intervention)

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Graphical abstract

29 pages, 5804 KiB

Open AccessSystematic Review

Risk of Nipah Virus Seroprevalence in Healthcare Workers: A Systematic Review with Meta-Analysis

by Matteo Riccò, Antonio Cascio, Claudio Costantino, Silvia Corrado, Ilaria Zanella, Pasquale Gianluca Giuri and Susanna Esposito

Viruses 2025, 17(1), 81; https://doi.org/10.3390/v17010081 - 9 Jan 2025

Abstract

Nipah virus (NiV) is a zoonotic pathogen with the potential to cause human outbreaks with a high case fatality ratio. In this systematic review and meta-analysis, available evidence on NiV infections occurring in healthcare workers (HCWs) was collected and critically appraised. According to [...] Read more.

Nipah virus (NiV) is a zoonotic pathogen with the potential to cause human outbreaks with a high case fatality ratio. In this systematic review and meta-analysis, available evidence on NiV infections occurring in healthcare workers (HCWs) was collected and critically appraised. According to the PRISMA statement, four medical databases (PubMed, CINAHL, EMBASE, and Scopus) and the preprint repository medRixv were inquired through a specifically designed searching strategy. A total of 2593 entries were identified; of them, 16 studies were included in qualitative and quantitative analysis detailing the outcome of NiV infection on HCWs and estimates of seroprevalence among healthcare professions. All studies reported data from Asian countries: Malaysia, Singapore, Bangladesh, India (States of Kerala and Bengal), and Philippines. Seroprevalence was estimated from seven studies in 0.00% (95%CI 0.00 to 0.10) for IgM-class antibodies and 0.08% (95%CI 0.00 to 0.72) for IgG class-antibodies, but four of the sampled studies did not report any seropositive cases. A case fatality ratio of 73.52% (95%CI 34.01 to 99.74) was calculated from 10 studies. In conclusion, the present study shows that NiV may result in a possible occupational infection among HCWs involved in managing incident cases. As most NiV outbreaks occur in limited resources settings, it is reasonable that even basic preventive measures (i.e., mandatory use of PPE and appropriate isolation of incident cases with physical distancing) may be quite effective in avoiding the occurrence of new infections among HCWs. Full article

(This article belongs to the Special Issue Emerging Zoonotic Paramyxoviruses)

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5 pages, 167 KiB

Open AccessEditorial

Perspective on the 65-Year Anniversary of the Discovery of Cytomegalovirus

by Edward S. Mocarski

Viruses 2025, 17(1), 80; https://doi.org/10.3390/v17010080 - 9 Jan 2025

Abstract

This volume presents research and reviews bringing forward new insights into cytomegalovirus (CMV) pathogenesis and biology; CMV is a herpesvirus that has long been recognized as being medically significant [...] Full article

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

10 pages, 836 KiB

Open AccessArticle

Prevalence, Molecular Epidemiology, and Clinical Characteristics of Human Bocavirus Among Patients with Acute Gastroenteritis in Northern Brazil During 2017–2022

by Yasmim Gabrielly Souza Sousa, Carolina Alcântara Maneschy, Carolina Costa Monteiro, João Victor Souza Rodrigues, Patrícia Santos Lobo, Dielle Monteiro Teixeira, Jones Anderson Monteiro Siqueira, Kenny Costa Pinheiro, Hugo Reis Resque, Luciana Damascena Silva, Sylvia Fátima dos Santos Guerra and Luana Silva Soares

Viruses 2025, 17(1), 79; https://doi.org/10.3390/v17010079 - 9 Jan 2025

Abstract

Acute gastroenteritis (AG) is a major illness in early childhood. Recent studies suggest a potential association between human bocavirus (HBoV) and AG. HBoV, a non-enveloped virus with a single-strand DNA genome, belongs to the Parvoviridae family. This study aimed to describe the frequency [...] Read more.

Acute gastroenteritis (AG) is a major illness in early childhood. Recent studies suggest a potential association between human bocavirus (HBoV) and AG. HBoV, a non-enveloped virus with a single-strand DNA genome, belongs to the Parvoviridae family. This study aimed to describe the frequency of HBoV in Northern Brazil using samples from patients with AG collected between 2017 and 2022. Fecal samples obtained from the viral gastroenteritis surveillance network at the Evandro Chagas Institute (IEC) were analyzed. Fecal suspensions (20%) were prepared, and the viral genome was extracted. PCR and nested-PCR were employed to detect HBoV, followed by nucleotide sequencing to identify viral types. Out of 692 samples, HBoV positivity was detected in 9.2% of cases (64/692). Genotypes HBoV-1, HBoV-2, HBoV-3, and HBoV-4 were found in 42.5% (17/40), 22.5% (9/40), 32.5% (13/40), and 2.5% (1/40) of the specimens, respectively. Co-infections with HBoV and other enteric viruses occurred in 48.3% (31/64) of cases, with RVA being the most frequent (31.2%, 20/64). The study results underscore the importance of continuous monitoring and further research to better understand the seasonality, coinfection patterns, and genetic variability of HBoV. Full article

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

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14 pages, 1813 KiB

Open AccessArticle

COVID-19 Vaccine Booster Dose Fails to Enhance Antibody Response to Omicron Variant in Reinfected Healthcare Workers

by Leire Fernández-Ciriza, Álvaro González, José Luis del Pozo, Alejandro Fernandez-Montero, Francisco Carmona-Torre, Paula Martínez de Aguirre, María del Mar Sarasa, Silvia Carlos and Gabriel Reina

Viruses 2025, 17(1), 78; https://doi.org/10.3390/v17010078 - 9 Jan 2025

Abstract

The emergence of new variants and diverse vaccination regimens have raised uncertainty about vaccine effectiveness against SARS-CoV-2. This study aims to investigate the impact of Omicron primo-/reinfection and primary vaccination schedules on the immunogenicity of an mRNA-based booster dose over a six-month period. [...] Read more.

The emergence of new variants and diverse vaccination regimens have raised uncertainty about vaccine effectiveness against SARS-CoV-2. This study aims to investigate the impact of Omicron primo-/reinfection and primary vaccination schedules on the immunogenicity of an mRNA-based booster dose over a six-month period. We conducted a prospective cohort study to assess the durability and level of antibodies of 678 healthcare workers fully vaccinated against COVID-19. They were categorized based on their primary vaccination regimen. Blood samples were collected before the booster dose and 1 and 6 months after. Significant Anti-S-RBD differences were found between previously infected and naïve volunteers (p = 0.01). Considering the initial vaccine schedules, mRNA-based vaccines displayed significant higher antibody production and longer persistence among both infected and naïve participants. After the booster dose, participants primoinfected with the Omicron variant exhibited higher antibody concentrations than those who experienced reinfection, even after 6 months of follow-up (22,545 and 9460 U/mL, respectively). Moreover, these groups showed the most pronounced disparity in antibody titers ratios between infected and uninfected individuals. Overall, the booster dose failed to enhance humoral response in individuals reinfected with the Omicron variant after receiving it. Hybrid immunity and mRNA-based vaccine initial schedules showed higher levels and longer persistence of antibodies. Full article

(This article belongs to the Special Issue Evaluation of COVID-19 Booster Vaccine Effects)

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16 pages, 746 KiB

Open AccessArticle

Bronchiolitis Severity Affects Blood Count and Inflammatory Marker Levels: A Real-Life Experience

by Antonella Gambadauro, Salvatore Mollica, Emanuela Rosa, Federica Xerra, Alessandra Li Pomi, Mariella Valenzise, Maria Francesca Messina, Agata Vitale, Eloisa Gitto, Malgorzata Wasniewska, Giuseppina Zirilli and Sara Manti

Viruses 2025, 17(1), 77; https://doi.org/10.3390/v17010077 - 9 Jan 2025

Abstract

Background: Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, [...] Read more.

Background: Bronchiolitis is the most common cause of lower respiratory tract infection (LRTI) in the first year of life. We analyzed the association between complete blood count (CBC), c-reactive protein (CRP), and novel inflammatory indexes (NLR, PLR, MLR, ELR, LMR, NPR, LPR, LNR, PNR, SII, SIRI) in predicting bronchiolitis severity at hospital admission. Methods: We retrospectively collected data from 95 infants hospitalized for bronchiolitis in a third-level hospital during three epidemic seasons. Five outcomes of severity were analyzed: BRAS; pediatric intensive care unit (PICU) admission; ventilatory support; intravenous (IV) rehydration; and length of stay (LOS). Results: Lower age and weight at admission were statistically associated with four of the five severity outcomes. Prolonged LOS (≥6 days) was associated with high values of total white blood cells, lymphocytes, and eosinophils. Only three inflammatory indexes (PLR, MLR, and PNR) showed a significant association with one outcome (prolonged LOS). A new index (RBC/AiW/1000) was statistically associated with each severity outcome for a value > 350. Conclusions: We proposed a comprehensive analysis of the association between CBC, CRP, and novel inflammatory indexes and bronchiolitis severity. RBC/AiW/1000 could represent a future predictive marker of disease severity at hospital admission in infants with bronchiolitis. Full article

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

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9 pages, 403 KiB

Open AccessCommunication

Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection

by Aura Temereanca, Luminita Ene, Gratiela Tardei, Camelia Grancea, Cristian L. Achim and Simona Ruta

Viruses 2025, 17(1), 76; https://doi.org/10.3390/v17010076 - 9 Jan 2025

Abstract

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally [...] Read more.

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.7% of participants, with lower levels correlating with longer cART exposure and better immunologic parameters. Patients with immunological treatment success (CD4 > 350 cells/mL) had significantly lower CMV IgG titers compared to those with suboptimal immune response to cART. In total, 78% of the tested patients had robust CMV-specific T-cell responses, measured by an IFN-γ release assay. A good immune response to treatment was significantly associated with CMV-specific cellular immunity: IFN-γ level was positively correlated with CD4 and CD8-T cell counts. No differences were observed between patients with suppressed/non-suppressed HIV viremia in terms of CMV humoral and cellular immune response. CMV DNA was detected in only 17% of participants, with lower levels among those with cART-induced immune recovery. The successful antiretroviral treatment with subsequent immunologic reconstitution may lead to restoration of CMV-specific immune responses and effective control of latent infection, limiting episodes of CMV reactivation in HIV-positive individuals. Full article

(This article belongs to the Special Issue Cascade of Care for HIV and Hepatitis)

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17 pages, 3559 KiB

Open AccessArticle

Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease

by Vincent N. Azzolino, Ala M. Shaqra, Akbar Ali, Nese Kurt Yilmaz and Celia A. Schiffer

Viruses 2025, 17(1), 75; https://doi.org/10.3390/v17010075 - 8 Jan 2025

Abstract

Enterovirus-D68 (EV68) continues to present as a global health issue causing respiratory illness and outbreaks associated with long-lasting neurological disease, with no antivirals or specific treatment options. The development of antiviral therapeutics, such as small-molecule inhibitors that _target conserved proteins like the enteroviral [...] Read more.

Enterovirus-D68 (EV68) continues to present as a global health issue causing respiratory illness and outbreaks associated with long-lasting neurological disease, with no antivirals or specific treatment options. The development of antiviral therapeutics, such as small-molecule inhibitors that _target conserved proteins like the enteroviral 3C protease, remains to be achieved. While various 3C inhibitors have been investigated, their design does not consider the potential emergence of drug resistance mutations. For other antivirals where resistance has been a challenge, we have demonstrated that the likelihood of resistance can be minimized by designing inhibitors that leverage the evolutionary constraints of the _target. Here, we characterize a series of 3C inhibitors against EV68-3C protease through enzyme inhibition, protein crystallography, and structural analysis. We have determined and analyzed three high-resolution inhibitor-bound crystal structures of EV68-3C protease, which revealed possible sites of resistance mutations, a key structural water molecule conserved during ligand binding, and the conformational flexibility of the catalytic histidine H40. This structural analysis combined with enzymatic assays provides insights for the rational design of inhibitors that are robust against resistance toward developing antiviral treatments for EV68 infections. Full article

(This article belongs to the Special Issue Structure-Guided Antiviral Discovery: From _target Validation to Drug Design to Candidate Selection)

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39 pages, 1385 KiB

Open AccessReview

A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection

by Aarti Tripathi, Shailendra Chauhan and Renu Khasa

Viruses 2025, 17(1), 74; https://doi.org/10.3390/v17010074 - 8 Jan 2025

Abstract

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest [...] Read more.

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy. Extensive research has been conducted in developing effective antivirals for flavivirus. Various approaches have been extensively utilized in clinical trials for antiviral development, _targeting virus entry, replication, polyprotein synthesis and processing, and egress pathways exploiting virus as well as host proteins. However, to date, no licensed antiviral drug exists to treat the diseases caused by these viruses. Understanding the mechanisms of host–pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis is highly warranted to foster the development of antivirals. This review provides an extensively detailed summary of the most recent advances in the development of antiviral drugs to combat diseases. Full article

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

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18 pages, 1948 KiB

Open AccessArticle

Genetic and Molecular Characterization of Avian Influenza A(H9N2) Viruses from Live Bird Markets (LBM) in Senegal

by Mamadou Malado Jallow, Moussa Moise Diagne, Marie Henriette Dior Ndione, Mamadou Aliou Barry, Ndiendé Koba Ndiaye, Davy Evrard Kiori, Marie Pedapa Mendy, Déborah Goudiaby, Gamou Fall, Malick Fall and Ndongo Dia

Viruses 2025, 17(1), 73; https://doi.org/10.3390/v17010073 - 8 Jan 2025

Abstract

Despite extensive experience with influenza surveillance in humans in Senegal, there is limited knowledge about the actual situation and genetic diversity of avian influenza viruses (AIVs) circulating in the country, hindering control measures and pandemic risk assessment. Therefore, as part of the “One [...] Read more.

Despite extensive experience with influenza surveillance in humans in Senegal, there is limited knowledge about the actual situation and genetic diversity of avian influenza viruses (AIVs) circulating in the country, hindering control measures and pandemic risk assessment. Therefore, as part of the “One Health” approach to influenza surveillance, we conducted active AIV surveillance in two live bird markets (LBMs) in Dakar to better understand the dynamics and diversity of influenza viruses in Senegal, obtain genetic profiles of circulating AIVs, and assess the risk of emergence of novel strains and their transmission to humans. Cloacal swabs from poultry and environmental samples collected weekly from the two LBMs were screened by RT-qPCR for H5, H7, and H9 AIVs. Subsequently, a subset of H9-positive samples was selected for whole sequencing. From December 2023 to October 2024, 499 samples were tested, and AIV was detected in 58.3% of them. Among these, A/H9N2 was the only subtype detected in both markets, with a detection rate of 47.7% (82/172) in Thiaroye and 35.3% (42/119) in Tilene, resulting in an overall positivity rate of 42.6% (124/291). Genome sequencing of 22 A/H9N2 isolates, including 11 poultry drinking water samples, 7 carcass wash water samples, 3 fecal samples, and 1 cloacal swab, yielded 7 complete and 15 partial genomic sequences. Phylogenetic analyses of the resulting sequences showed that the A/H9N2 isolates obtained in this study formed a monophyletic cluster and were closely related to the Senegalese human strain (A/Senegal/0243/2019) identified through the national influenza sentinel surveillance program. These strains were also closely related to the A/H9N2 viruses of the G1 lineage circulating in neighboring countries, suggesting cross-border transmission. The A/H9N2 strains carried the low pathogenicity RSSR/GLF motif at the HA cleavage site and possessed several key amino acid mutations, including HA-I155T and HA-Q226L, which are associated with human host adaptation, PB2-T105V, PB2-A661T, and PB2-A588V, which are linked to the human-to-human transmission and increased polymerase activity, NS2-T14M, NS2-M100I, NS1-I106M, NS1-V222M, NS1-E223A, NS1-I226V, NS1-E227G, and NS1-P228S, which are known to alter virulence (increased or reduced) in humans or mice, and M2-S31N, which promotes drug resistance. Seven potential N-glycosylation sites were predicted in the HA protein and six in the NA protein. The selection pressure analysis revealed that the A/H9N2 isolates were primarily under neutral evolution or purifying selection pressure. Overall, our findings highlight the potential for cross-species transmission of Senegalese A/H9N2 viruses, emphasizing the need for sustained monitoring of these viruses in both animal and human populations. Full article

(This article belongs to the Special Issue Controlling Zoonotic Viral Diseases from One Health Perspective 2025)

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16 pages, 1324 KiB

Open AccessReview

Emerging Roles of TRIM56 in Antiviral Innate Immunity

by Dang Wang and Kui Li

Viruses 2025, 17(1), 72; https://doi.org/10.3390/v17010072 - 7 Jan 2025

Abstract

The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. [...] Read more.

The tripartite-motif protein 56 (TRIM56) is a RING-type E3 ubiquitin ligase whose functions were recently beginning to be unveiled. While the physiological role(s) of TRIM56 remains unclear, emerging evidence suggests this protein participates in host innate defense mechanisms that guard against viral infections. Interestingly, TRIM56 has been shown to pose a barrier to viruses of distinct families by utilizing its different domains. Apart from exerting direct, restrictive effects on viral propagation, TRIM56 is implicated in regulating innate immune signaling pathways that orchestrate type I interferon response or autophagy, through which it indirectly impacts viral fitness. Remarkably, depending on viral infection settings, TRIM56 either operates in a canonical, E3 ligase-dependent fashion or adopts an enzymatically independent, non-canonical mechanism to bolster innate immune signaling. Moreover, the recent revelation that TRIM56 is an RNA-binding protein sheds new light on its antiviral mechanisms against RNA viruses. This review summarizes recent advances in the emerging roles of TRIM56 in innate antiviral immunity. We focus on its direct virus-restricting effects and its influence on innate immune signaling through two critical pathways: the endolysosome-initiated, double-stranded RNA-sensing TLR3-TRIF pathway and the cytosolic DNA-sensing, cGAS-STING pathway. We discuss the underpinning mechanisms of action and the questions that remain. Further studies understanding the complexity of TRIM56 involvement in innate immunity will add to critical knowledge that could be leveraged for developing antiviral therapeutics. Full article

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

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15 pages, 22720 KiB

Open AccessCommunication

Conserved Nuclear Localization Signal in NS2 Protein of Bombyx Mori Bidensovirus: A Potential Invertebrate ssDNA Virus Trait

by Qian Yu, Jiaxin Yan, Ying Chen, Jinfeng Zhang, Qi Tang, Feifei Zhu, Lindan Sun, Shangshang Ma, Xiaoyong Liu, Keping Chen and Qin Yao

Viruses 2025, 17(1), 71; https://doi.org/10.3390/v17010071 - 6 Jan 2025

Abstract

Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, [...] Read more.

Bombyx mori bidensovirus (BmBDV), a significant pathogen in the sericulture industry, holds a unique taxonomic position due to its distinct segmented single-stranded DNA (ssDNA) genome and the presence of a self-encoding DNA polymerase. However, the functions of viral non-structural proteins, such as NS2, remain unknown. This protein is hypothesized to play a role in viral replication and pathogenesis. To investigate its structure and function, we employed phylogenetic analysis, subcellular localization, mutational analysis, and a dual-luciferase reporter system to characterize the nuclear localization signal (NLS) within NS2 and its effect on viral promoter activity. Additionally, co-immunoprecipitation and mass spectrometry were utilized to identify host proteins interacting with NS2. We identified a functional bipartite NLS in NS2, validated the combination pattern of key amino acids, and demonstrated its role in regulating viral promoter activity. Furthermore, we identified potential NLSs in NS2 homologs in other invertebrate ssDNA viruses based on sequence analysis. We also revealed interactions between NS2 and host nuclear transport proteins, suggesting that it plays a role in nuclear transport and viral replication. This research underscores the importance of NS2’s NLS in BmBDV’s life cycle and its potential conservation across invertebrate ssDNA viruses, providing insights into virus–host interactions and avenues for antiviral strategy development. Full article

(This article belongs to the Special Issue Virus-Host Protein Interactions)

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11 pages, 1215 KiB

Open AccessArticle

Bacteriophage and Phage-Encoded Depolymerase Exhibit Antibacterial Activity Against K9-Type Acinetobacter baumannii in Mouse Sepsis and Burn Skin Infection Models

by Alexander I. Borzilov, Nikolay V. Volozhantsev, Olga V. Korobova, Lyubov V. Kolupaeva, Evgenia S. Pereskokova, Tatiana I. Kombarova, Mikhail M. Shneider, Konstantin A. Miroshnikov, Ivan A. Dyatlov and Anastasia V. Popova

Viruses 2025, 17(1), 70; https://doi.org/10.3390/v17010070 - 6 Jan 2025

Abstract

Acinetobacter baumannii is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn [...] Read more.

Acinetobacter baumannii is a widely distributed nosocomial pathogen that causes various acute and chronic infections, particularly in immunocompromised patients. In this study, the activities of the K9-specific virulent phage AM24 and phage-encoded depolymerase DepAPK09 were assessed using in vivo mouse sepsis and burn skin infection models. In the mouse sepsis model, in the case of prevention or early treatment, a single K9-specific phage or recombinant depolymerase injection was able to protect 100% of the mice after parenteral infection with a lethal dose of A. baumannii of the K9-type, with complete eradication of the pathogen. In the case of delayed treatment, mouse survival decreased to 70% when injected with the phage and to 40% when treated with the recombinant enzyme. In the mouse burn skin infection model, the number of A. baumannii cells on the surface of the wound and in the deep layers of the skin decreased by several-fold after treatment with both the K9-specific phage and the recombinant depolymerase. The phage and recombinant depolymerase were highly stable and retained activity under a wide range of temperatures and pH values. The results obtained contribute to expanding our understanding of the in vivo therapeutic potential of specific phages and phage-derived depolymerases interacting with A. baumannii of different capsular types. Full article

(This article belongs to the Special Issue Phage-Bacteria Interplay in Health and Disease, Second Edition)

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15 pages, 2294 KiB

Open AccessArticle

Tenofovir and Doravirine Are Potential Reverse-Transcriptase Analogs in Combination with the New Reverse-Transcriptase Translocation Inhibitor (Islatravir) Among Treatment-Experienced Patients in Cameroon: Designing Future Treatment Strategies for Low- and Middle-Income Countries

by Alex Durand Nka, Yagai Bouba, Wilfried Rooker Tsapi Lontsi, Davy-Hyacinte Gouissi Anguechia, Georges Teto, Aude christelle Ka’e, Ezechiel Ngoufack Jagni Semengue, Collins Ambe Chenwi, Désiré Takou, Lum Forgwei, Tatiana Anim-Keng Tekoh, Aurelie Minelle Kengni Ngueko, Bernadette Bomgning Fokou, Jeremiah Efakika Gabisa, Michel Carlos Tommo Tchouaket, Willy Leroi TognaPabo, Derrick Tambe Ayuk Ngwese, Jacky Njiki Bikoi, Daniele Armenia, Vittorio Colizzi, Marcel Yotebieng, Nicaise Ndembi, Maria-Mercedes Santoro, Francesca Ceccherini-Silberstein, Carlo-Federico Perno, Alexis Ndjolo and Joseph Fokam Show full author list Hide full author list

Viruses 2025, 17(1), 69; https://doi.org/10.3390/v17010069 - 6 Jan 2025

Abstract

Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL [...] Read more.

Islatravir (ISL) is a novel antiretroviral that inhibits HIV-1 reverse transcriptase translocation. The M184V mutation, known to reduce ISL’s viral susceptibility in vitro, could arise from prolonged exposure to nucleoside reverse transcriptase inhibitors (NRTI) (3TC). This study evaluated the predictive efficacy of ISL and identified potentially active antiretrovirals in combination among treatment-experienced patients in Cameroon, where NRTIs (3TC) have been the backbone of ART for decades now. Although ISL is a long-acting antiretroviral, it will provide other therapeutic options in combination with other reverse transcriptase inhibitors that remain effective. We analyzed 1170 HIV-1 sequences from patients failing first-, second-, and third-line ART using the CIRCB Antiviral Resistance Evaluation (CIRCB-CARE) database. Drug resistance mutations (DRMs) were interpreted using Stanford HIVdb.v9, and covariation patterns between M184V and major NRTI/NNRTI DRMs were assessed. The study population, with a median age of 40 years, showed a high prevalence of resistance to NRTIs (77.4%) and NNRTIs (49.2%). The most frequent NRTI DRMs were M184V/I (83.3%), M41L (25.0%), and T215FY (36.8%), while common NNRTI DRMs included K103NS (53.3%), Y181CIV (27.7%), and G190ASE (22.2%). In first-line ART failure, M184V significantly covaried with K70R, L74I, and M41L for NRTIs and K103N and G190A for NNRTIs. In second-line failure, the covariation with M184V extended to T215Y, M41L, and D67N for NRTIs and G190A, K103N, and K103S for NNRTIs. No significant covariation with M184V was observed in third-line treatment failures. Based on these covariations and on the effect of these mutations on available anti-HIV drugs, TDF (partial efficacy) and Doravirine (fully active) were identified as potentially suitable candidates in combination with ISL among patients failing the first, second, and third lines, and could serve as a valuable therapeutic option in LMICs facing similar treatment challenges. Full article

(This article belongs to the Special Issue Antiviral Drugs and Biologics _targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)

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22 pages, 3557 KiB

Open AccessReview

Impact of COVID-19 on Ocular Surface Health: Infection Mechanisms, Immune Modulation, and Inflammatory Responses

by Duliurui Huang, Weixia Xuan and Zhijie Li

Viruses 2025, 17(1), 68; https://doi.org/10.3390/v17010068 - 6 Jan 2025

Abstract

COVID-19, caused by SARS-CoV-2, has presented formidable challenges to global health since its emergence in late 2019. While primarily known for respiratory symptoms, it can also affect the ocular surface. This review summarizes the effects of SARS-CoV-2 on ocular surface immunity and inflammation, [...] Read more.

COVID-19, caused by SARS-CoV-2, has presented formidable challenges to global health since its emergence in late 2019. While primarily known for respiratory symptoms, it can also affect the ocular surface. This review summarizes the effects of SARS-CoV-2 on ocular surface immunity and inflammation, focusing on infection mechanisms, immune responses, and clinical manifestations. Ocular symptoms, though uncommon, include conjunctivitis, dry eye, and blurred vision. SARS-CoV-2 binds to ACE2 receptors in ocular surface epithelial cells, facilitating viral entry, replication, and local dissemination. The innate immune responses involving corneal epithelial cells and immune cells are discussed, alongside mechanisms of antigen presentation and adaptive immunity. The review also examines the roles of cytokines and chemokines in mediating ocular surface inflammation and explores the impact of cytokine storms and chronic inflammation on ocular health. Additionally, the interplay between systemic and ocular immune responses is highlighted, analyzing how systemic COVID-19 inflammation influences ocular surface health. These insights underscore the broader implications of COVID-19 beyond localized ocular infection. By consolidating current findings, this review aims to guide preventive and therapeutic strategies while identifying directions for future research to mitigate the ocular consequences of COVID-19. Full article

(This article belongs to the Special Issue Ocular Diseases in Viral Infection)

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18 pages, 5451 KiB

Open AccessArticle

Functional Verification of Differentially Expressed Genes Following DENV2 Infection in Aedes aegypti

by Xiaoli Chen, Xinyu Zhou, Xiaoxue Xie, Bo Li, Teng Zhao, Haotian Yu, Dan Xing, Jiahong Wu and Chunxiao Li

Viruses 2025, 17(1), 67; https://doi.org/10.3390/v17010067 - 6 Jan 2025

Abstract

The dengue virus (DENV) is primarily transmitted by Aedes aegypti. Investigating genes associated with mosquito susceptibility to DENV2 offers a theoretical foundation for _targeted interventions to regulate or block viral replication and transmission within mosquitoes. Based on the transcriptomic analyses of the [...] Read more.

The dengue virus (DENV) is primarily transmitted by Aedes aegypti. Investigating genes associated with mosquito susceptibility to DENV2 offers a theoretical foundation for _targeted interventions to regulate or block viral replication and transmission within mosquitoes. Based on the transcriptomic analyses of the midgut and salivary glands from Aedes aegypti infected with DENV2, alongside analyses of Aag2 cell infections, 24 genes potentially related to the regulation of Aedes aegypti infection with DENV2 were selected. By establishing transient transfection and overexpression models of Aedes aegypti Aag2 cells, and mosquito _target gene interference models, the difference in viral load before and after treatment was compared, and the effects of DEGs on viral replication were evaluated. After overexpressing 24 DEGs in Aag2 cells, 19 DEGs showed a significant difference in DENV2 RNA copies in the cell supernatant (p < 0.05). In adult mosquitoes, knocking down defensin-A, defensin-A-like, and SMCT1 respectively reduced the DENV2 RNA copies, while knocking down UGT2B1 and ND4 respectively increased the DENV2 RNA copies. In this study, to assess the role of genes related to DENV2 replication, and transient transfection and overexpression models in Aag2 cells and mosquito gene knockdown models were established, and five genes, defensin-A, defensin-A-like, SMCT1, UGT2B1, and ND4, were found to have an impact on the replication of DENV2, providing a reference basis for studying the complex mechanism of mosquito–virus interactions. Full article

(This article belongs to the Section Invertebrate Viruses)

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16 pages, 1524 KiB

Open AccessReview

Effect of Hepatitis E Virus on the Male Reproductive System: A Review of Current Evidence

by Ahmed A. Kotb, Mohamed A. El-Mokhtar and Ibrahim M. Sayed

Viruses 2025, 17(1), 66; https://doi.org/10.3390/v17010066 - 5 Jan 2025

Abstract

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several [...] Read more.

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females. Several studies have investigated the impact of HEV on the male reproductive system; however, the available data are limited and conflicting. Assessment of the patients’ ejaculates/semen samples revealed that HEV particles are excreted in these fluids in cases of chronic infection but not acute infection. The excreted HEV particles are infectious to in vivo animal models and in vitro cell culture. However, the effect of HEV infection on male infertility is not confirmed. One study including human samples showed male infertility associated with HEV genotype 4 infection. Studies of HEV infection in animal models such as pigs, gerbils, and mice showed that HEV infection caused distortion on the testes, damage of the blood–testis barrier, and induction of inflammatory responses leading to abnormalities in the sperm. The excretion of HEV in the semen fluids raises concerns about HEV transmission via sexual transmission. However, all available data do not confirm the transmission of HEV through sexual intercourse. This review aims to summarize and critically assess the available studies investigating the influence of different HEV genotypes on the male reproductive system, providing insights into whether HEV contributes to reproductive impairment in men. Full article

(This article belongs to the Special Issue Hepatitis Viral Infections, Pathogenesis and Therapeutics)

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15 pages, 577 KiB

Open AccessReview

Are You My Host? An Overview of Methods Used to Link Bacteriophages with Hosts

by Paul Hyman

Viruses 2025, 17(1), 65; https://doi.org/10.3390/v17010065 - 5 Jan 2025

Abstract

Until recently, the only methods for finding out if a particular strain or species of bacteria could be a host for a particular bacteriophage was to see if the bacteriophage could infect that bacterium and kill it, releasing progeny phages. Establishing the host [...] Read more.

Until recently, the only methods for finding out if a particular strain or species of bacteria could be a host for a particular bacteriophage was to see if the bacteriophage could infect that bacterium and kill it, releasing progeny phages. Establishing the host range of a bacteriophage thus meant infecting many different bacteria and seeing if the phage could kill each one. Detection of bacterial killing can be achieved on solid media (plaques, spots) or broth (culture clearing). More recently, additional methods to link phages and hosts have been developed. These include methods to show phage genome entry into host cells (e.g., PhageFISH); proximity of phage and host genomes (e.g., proximity ligation, polonies, viral tagging); and analysis of genomes and metagenomes (e.g., CRISPR spacer analysis, metagenomic co-occurrence). These methods have advantages and disadvantages. They also are not measuring the same interactions. Host range can be divided into multiple host ranges, each defined by how far the phage can progress in the infection cycle. For example, the ability to effect genome entry (penetrative host range) is different than the ability to produce progeny (productive host range). These different host ranges reflect bacterial defense mechanisms that block phage growth and development at various stages in the infection cycle. Here, I present a comparison of the various methods used to identify bacteriophage-host relationships with a focus on what type of host range is being measured or predicted. Full article

(This article belongs to the Special Issue Bacteriophage Diversity)

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