Viruses-Basel最新文献

The Orthoflavivirus genus includes a variety of human-pathogenic, mosquito-borne flaviviruses (MBFs) including dengue, Zika, and West Nile viruses, which pose significant global public health threats. Insect-specific flaviviruses (ISFs) are another group within the genus that exclusively replicate in mosquitoes and are incapable of infecting vertebrates. ISFs have recently attracted growing research interest due to their potential applications in vaccine development. In addition, multiple studies have demonstrated that prior infection with ISFs such as Palm Creek virus and Binjari virus can suppress subsequent infection with human-pathogenic MBFs. This phenomenon, known as superinfection exclusion (SIE), opens the avenue for the potential applications of ISFs in MBF transmission control. This prompted a growing number of studies into ISFs and their interactions with MBFs in mosquito hosts. In this review, we provide an overview on ISFs, with a particular emphasis on the capacity of different ISFs to cause SIE, the current insights into the mechanisms of this phenomenon, and the potential use of ISFs in the SIE-based biocontrol strategies.

Influenza A viruses exhibit broad host tropism, infecting multiple species including humans, avian species, and swine. Swine influenza virus (SIV), while primarily circulating in porcine populations, demonstrates zoonotic potential with sporadic human infections. In this investigation, we identified two H1N1 subtype swine influenza A virus strains designated A/swine/China/SD6591/2019(H1N1) (abbreviated SD6591) and A/swine/China/SD6592/2019(H1N1) (abbreviated SD6592) in Shandong Province, China. The GenBank accession numbers of the SD6591 viral gene segments are PV464931-PV464938, and the GenBank accession numbers corresponding to each of the eight SD6592 viral gene segments are PV464939-PV464946. Phylogenetic and recombination analyses suggest potential evolutionary differences between the isolates. SD6591 displayed a unique triple-reassortant genotype: comparative nucleotide homology assessments demonstrated that the PB2, PB1, NP, NA, HA, and NEP genes shared the highest similarity with classical swine-origin H1N1 viruses. In contrast, SD6592 maintained genomic conservation with previously characterized H1N1 swine strains, although neither of these two isolates exhibited significant intrasegmental recombination events. Through comprehensive sequence analysis of these H1N1 SIVs, this study provides preliminary insights into their evolutionary history and underscores the persistent risk of cross-species transmission at the human-swine interface. These findings establish an essential foundation for enhancing national SIV surveillance programs and informing evidence-based prevention strategies against emerging influenza threats.

Our laboratory identified the susceptible allelic variant of equine CXCL16 protein (EqCXCL16S) as an entry receptor for equine arteritis virus (EAV). However, EAV has a broad host cell tropism and infects cells that lack EqCXCL16S. Thus, we hypothesized that EAV interacts with other host cell protein(s) that facilitate EAV infection. A virus overlay protein-binding assay in combination with a Far-Western blot from EAV-susceptible equine pulmonary artery endothelial cells (EECs) and equine dermal fibroblasts (E. Derm) identified a 57 kDa protein, present in the membrane fraction of the protein lysate, as a possible EAV-binding protein. Subsequent LC-MS/MS analysis identified this 57 kDa protein as vimentin. Screening of different mammalian cell lines has shown that only cells expressing vimentin are susceptible to EAV infection. Pre-treatment of EECs with an anti-vimentin polyclonal antibody and Withaferin A partially inhibit EAV infection. Finally, the overexpression of equine vimentin (EqVim) in HEK-293 cells increases their susceptibility to EAV infection. Overall, our data strongly indicate that EAV binds to the host cell protein equine vimentin, which actively participates in EAV infection, potentially serving as an attachment factor. The data suggest that EAV interacts with various host cell proteins to achieve its diverse cell tropism.

Sexual violence against women is a global issue with profound health consequences, including elevated HIV risk due to genital tract inflammation and injury. However, limited research has examined the influence of mental health on HIV-related immunity after violence. We analyzed longitudinal data from female survivors of past-month rape (N = 25) to explore associations between mental health (perceived stress, depression, post-traumatic stress disorder [PTSD], and resilience) and HIV-associated immune biomarkers in the female genital tract. In bivariate analyses, mental health improved over the three-month follow-up period. Immune biomarker levels remained largely stable, except for TNF-α and SLPI. At baseline, depression was significantly correlated with TNF-α, IL-6, and IL-1β. In regression analyses, depression was associated with TNF-α (β = -0.133 to -0.152) and IL-6 (β = -0.171 to -0.207). PTSD was significantly associated with IL-1α (β = 0.576 to 1.681). Depression and resilience were negatively associated with percent HIV inhibition in adjusted models. These findings suggest that depression and PTSD are associated with genital tract inflammation following sexual violence, which may compromise mucosal immunity and enhance HIV risk. This highlights the importance of integrated mental health and immunological care for survivors and the need for further research into psychoneuroimmune pathways influencing HIV risk after trauma.

Background: The enhanced sensitivity of next-generation sequencing (NGS) for assessing hepatitis B virus (HBV) quasispecies heterogeneity over clone-based sequencing (CBS) is well documented. However, its comparative reliability for genotype determination remains an open question. Objective: This study aimed to directly compare the performance of NGS and CBS for genotyping HBV using the entire viral genome. Methods: We selected five challenging clinical samples that previously could not be subgenotyped or showed conflicting results when using direct sequencing of the S open reading frame (ORF). The full HBV genome from these subjects was amplified and then analyzed in parallel by both NGS and CBS. Phylogenetic analysis was subsequently used to assign genotypes. Results: Both methods identified a range of genotypes, including B, C, and I, as well as aberrant and recombinant forms. For three of the five subjects, genotyping results were identical between the two platforms. In the remaining two cases, however, CBS revealed greater complexity, identifying additional subgenotypes and recombinant/aberrant strains not detected by NGS. Notably, for three individuals, the genotypes determined by both modern methods contradicted earlier results from 2011 based on direct S ORF sequencing. Furthermore, the specific mutations detected were incongruent between the platforms, with CBS identifying a higher number of variants than NGS. Conclusions: Our findings indicate that genotyping results from NGS and CBS can be discordant. Contrary to expectations, CBS may uncover more genetic diversity, including a greater number of subgenotypes and mutations, than NGS in certain contexts. The study also confirms that genotyping based solely on direct sequencing of the S ORF can be unreliable and lead to misclassification.

In the original publication [...].

Vif and Vpr are HIV-1 accessory proteins that create optimal conditions for viral replication. They are considered as potential targets for the development of therapeutic agents. Natural amino acid substitutions in these proteins have previously been associated with disease progression. The aim of this study was to analyze the genetic diversity of Vif and Vpr in HIV-1 group M clades. A total of 5286 sequences were downloaded and analyzed. For 37 clades in group M, the consensus sequences, amino acid natural variation, and clade-specific amino acid residue substitutions (CSSs) were evaluated. Structural analysis and modeling of consensus sequences were performed for subtypes A1, B, C, and D. The average conservation degree in the HIV-1 group M was 86.4% for Vif and 91.3% for Vpr. In both proteins, the lowest amino acid diversity was observed in sub-subtype A6, and the highest in subtype B. In consensus sequences, the substitutions, which might influence pathogenesis, have been determined: in Vif-22H (11_cpx, 91_cpx) and 136P (A6, 01_AE, 15_01B, 59_01B, 89_BF1, 103_01B, 111_01C, 133_A6B), in Vpr-41N (06_cpx) and 55A (B, 07_BC, 35_01D, 56_cpx, 66_cpx, 66_BF1, 71_BF1, 85_BC, 137_0107). In functional motifs, CSSs associated with changes in the chemical properties of amino acid residues were noted. These findings could be taken into account for the development of therapeutic drugs in the future. No correlation was observed between the subtypes and the spatial organization of the oligomeric structures of Vif and Vpr. Using the structural analysis and modeling, it has been shown for the first time that Vif can interact with APOBEC3G as an oligomer.

The HIV epidemic in Romania started in the late eighties with a large cohort of children nosocomially infected with subtype F1 strains, in parallel with sexual transmission. The purpose of the present study was to investigate the transmitted drug resistance (TDR), subtype distribution, and transmission clusters among persons diagnosed with HIV between 2019 and 2022 in Romania. The prototype of a person recently diagnosed with HIV in Romania is male, 20-50 years old, a late presenter, infected with F1, B, or A subtype. The rate of TDR varied over time, from 5% in 2019 to 15% in 2022. TDR affected mainly the first generation of NNRTIs and the PI class. The rate of late presentation was almost 60%, with 35% of persons qualifying as very late presenters. Subtype F1 is still preponderant in Romania, whereas other subtypes (B, A) and recombinants account for a quarter of HIV-1 new cases. Several transmission networks were identified in the study population, two of them associated with TDR in subtypes F1 and A1. The largest cluster consisted of 26 sequences, originating from Western Romania and introduced around 2007. Molecular clock analysis indicated different origin time points for different clusters, with the most recent in subtypes A1 and B, and the oldest in subtype F1. In conclusion, the HIV-1 epidemic in Romania is currently driven by sexual transmission, with MSM contribution continuously rising in recent years; there are also increases in TDR and the circulation of HIV-1 strains other than F1 (subtype B, A, recombinants).

Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission occurs principally through bites from infected dogs and although multiple mammalian species are permissive to RV, transmission from them or from symptomatic humans is rare. To overcome the limitations posed by the requirement of biosafety level-3 (BSL-3) containment for live virus culture, we established a replication-deficient vesicular stomatitis virus (VSV) pseudovirus expressing the Rabies-G (RV-G) protein and a multiplexed Luminex immunoassay for quantifying anti-rabies antibodies in equine sera. The purified pseudovirus exhibited robust luciferase activity and was able to infect multiple mammalian cell lines, although with variable efficiency. Using hyper-immunized equine serum, we observed a strong correlation (ρ > 0.9, p < 0.001) between binding antibody titers measured by the Luminex assay with neutralizing antibody titers determined using the pseudovirus-based neutralization assay. These assays provide a safe, quantitative, and BSL-2-compatible platform for rabies serological evaluation and vaccine testing.

Vaccination has been a cornerstone of the public health response to the COVID-19 pandemic, particularly in protecting older and frail populations. A detailed characterization of antibody titer dynamics and their determinants represents a crucial step toward optimizing vaccination strategies. However, antibody titers are bounded within assay-specific limited intervals and often display skewness and intra-subject correlation, which limit the suitability of conventional modeling approaches. We analyzed longitudinal antibody titer data from 608 residents and staff members of five nursing homes in Calabria (southern Italy) using beta-generalized linear mixed models (β-GLMMs). This framework enabled simultaneous modeling of the mean humoral response (μ), precision parameter (ϕ), and probability of achieving the maximum immune response (α), thereby providing a comprehensive assessment of factors influencing immune dynamics. Two distinct patterns of antibody titer evolution were identified. Among nursing home residents, stroke was associated with higher antibody concentrations, whereas atrial fibrillation, lower body mass index, non-Alzheimer's dementia, and chronic obstructive pulmonary disease were linked to reduced responses. The β-GLMM approach allowed for a more accurate identification of demographic and clinical determinants compared with traditional methods. These findings underscore the utility of β-GLMMs for analyzing bounded longitudinal immunological data and highlight key factors shaping vaccine-induced immunity. Such insights may lead to more tailored immunization strategies in vulnerable older populations.