Virology Journal最新文献

Influenza A virus remains a persistent threat, continuously evolving and contributing to seasonal epidemics and potential pandemics. In this study, we analyzed clinical samples collected from pediatric patients in Shanghai between 2022 and 2023, following the SARS-CoV-2 pandemic, to assess the genetic diversity of circulating influenza A virus strains. Out of 88 clinical samples that were positive for influenza A virus, seven isolates were successfully cultured and subjected to whole-genome sequencing. Whole-genome sequencing was performed using the Illumina high-throughput sequencing platform, while missing genomic segments, which were identified in the whole-genome sequence of isolates, were later amplified via standard PCR and Sanger sequencing. Phylogenetic analysis revealed a significant divergence between H3N2 strains from 2023 to those from 2022, suggesting a potential decline in vaccine efficacy over successive seasons. A H1N1 strain isolated from 2022 exhibited close genetic similarity to the vaccine strain. Mutational analysis identified key substitutions in the hemagglutinin and neuraminidase regions, including the I222V mutation in the neuraminidase segment of sample B623080303, which is associated with strong resistance to oseltamivir and peramivir. Another highly drug-resistant N206D mutation in the hemagglutinin region, detected in four clinical isolates, was found to alter host specificity by reducing binding affinity to human-like α2,6-linked receptors while increasing affinity for avian-like α2,3-linked receptors, thereby influencing host adaptation dynamics. The findings provide critical insights into the evolutionary trends of influenza A virus strains post-COVID-19 pandemic and their potential implications for vaccine effectiveness and antiviral resistance.

Backgrounds &aims: Nucleos(t)ide analog (NAs) treatment achieves limited HBsAg loss rates; switching to or adding Peginterferon (PegIFN) therapy may improve outcomes. This study aimed to evaluate the efficacy of adding PegIFNα-2b therapy in chronic hepatitis B (CHB) patients who are virally suppressed by NAs.

Method: 250 CHB patients on NAs treatment with HBsAg < 1500 IU/mL, serum HBV DNA < 20 IU/mL, and ALT ≤ 1.5 × ULN were enrolled. Patients continued their NAs regimen and initiated PegIFNα-2b (180 µg/week) for 48 weeks, with follow-up until week 72. In addition to routine biochemistry, HBsAg and HBV RNA levels were measured at each visit; HBcrAg was assessed at baseline, week 12, and week 24.

Results: 214 patients completed 48 weeks of PegIFNα-2b therapy, and 34.6% achieved HBsAg loss at week 72. Lower baseline HBsAg was associated with higher rates of HBsAg clearance. Specifically, patients with baseline HBsAg < 10 IU/mL and 10-100 IU/mL achieved HBsAg clearance rates of 76.2% and 45.5% at week 72, respectively. In univariate analysis, baseline HBsAg and its decline at week 12 demonstrated the strongest predictive performance for HBsAg loss, while younger age and higher ALT were also associated with HBsAg clearance. However, in multivariate analysis, only age and HBsAg decline at week 12 remained independent predictors of HBsAg loss.

Conclusions: CHB patients with low HBsAg levels and virologic suppression on NAs can achieve significant HBsAg loss after adding PegIFNα-2b. A two-step strategy based on baseline HBsAg and week-12 HBsAg decline may aid patient selection and treatment optimization.

Background: West Nile virus (WNV) is primarily transmitted by the bite of Culex mosquitoes, but other mechanisms, such as blood transfusion, have also been described. Since its identification in the Americas in 1999, WNV has circulated consistently in the United States of America (USA); however, although WNV has been detected in humans in South America, no major outbreaks have occurred in more than 20 years. One of the hypotheses to explain this difference is the underdiagnosis of the infection. In Mexico, nine isolated cases have been officially reported since 2003 despite its proximity to the USA. In this study, we aim to demonstrate the circulation of WNV in blood donors from a northern border city of Mexico.

Methods: Between August and September of 2023, 86 serum samples from volunteer blood donors were collected to determine anti-WNV Immunoglobulin (Ig) G using a commercial enzyme-linked immunosorbent assay (ELISA) kit. In a subgroup of 44 samples, anti-WNV IgM was determined. To corroborate the IgM results, nucleic acid amplification tests (NAAT) were performed to determine RNA of WNV, Dengue and Zika. The participants were questioned about the history of travel to the USA; all of them were residents of the city of Nogales, Sonora, located on the border with the state of Arizona. For the comparison of seronegative and seropositive donor groups, the Chi-square test and Mann-Whitney U test were used for qualitative and quantitative variables, respectively. Additionally, a spatial analysis of seropositive cases was conducted.

Results: One sample was reactive to anti-WNV IgM and IgG; however, all NAAT results were negative. In addition, 19 samples were reactive for IgG, and no statistically significant differences were found between the groups. Seropositive cases showed a geographic pattern of clustering on the outskirts of the city, in areas with low population density.

Conclusions: Our results strongly suggest recent WNV circulation among residents from the northern border of Mexico. The lack of differences regarding the history and frequency of travel to the USA suggests that contact with the virus occurs in Mexico and that the low reported circulation in the region represents an underdiagnosis of the disease.

Background: Avidity assays often misclassify chronic HIV-1 infection as recent HIV-1 infection (false recency rate), especially in participants on antiretroviral therapy. The aim of this study was to use Shannon entropy to evaluate HIV-1 group-specific antigen (Gag) sequence diversity for the prediction of recent HIV-1 infections.

Methods: This was a retrospective study that characterised the complete HIV-1 Gag using Sanger sequences obtained from participants with confirmed recent or chronic HIV-1 infection. Shannon entropy was calculated for the entire HIV-1 Gag amino acid (aa) sequence (501aa) and sliding window analysis was computed at intervals of 100aa each. This was followed by searching for aa sites that exhibited a different distribution of mutations between recent and chronic HIV-1 infection stages. Reference sequences were obtained from GenBank and the Los Alamos HIV database to verify the findings obtained from study sequences.

Results: Forty-seven participants with a mean age of 28.7 years (18 - 44) were enrolled, and fourteen (30%) of them had recent HIV-1 infection. Shannon entropy analysis showed a significantly higher aa diversity in chronic HIV-1 infection compared to recent HIV-1 infection (p = 0.0003). Analysis of sliding windows led to identification of four aa positions; S54, E55, I256, and S451; with different pattern of distribution between recent and chronic HIV-1 infection stages; however statistical significance was only observed for three of these aa, p values = 0.094, 0.027, 0.027 and 0.045, respectively. The performance of these informative sites for detection of recent HIV-1 infection in study sequences ranged from 71-86%, however, they had a high false recency rate (FRR) ranging from 39%-52%. Similar performance was observed in reference sequences. The combination of some informative aa sites reduced FRR in study sequences to below 24%.

Conclusions: Our data show that a Gag-based molecular strategy can be used to detect recent HIV-1 infections where Gag sequences are available. However, the results would have to be interpreted with caution due to an association with a high FRR. Further studies are needed to develop a molecular-based strategy with better performance for detection of recent HIV-1 infections.

Background: Mother-to-child transmission (MTCT) is the primary cause of hepatitis B virus (HBV) infection. Antiviral therapy is crucial to reduce MTCT for pregnant women with high viremia. Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are the first-line antiviral drugs for hepatitis B. This study aimed to evaluate the effectiveness and safety of TAF and TDF in preventing HBV MTCT among treatment-naïve mothers.

Methods: A total of 290 pregnant women with HBsAg positive for > 6 months, and HBV DNA ≥ 2 × 10^5 IU/ml or HBeAg positive were enrolled. Mothers received either TDF or TAF therapy and newborns received hepatitis B immunoglobulin and recombinant yeast hepatitis B vaccine. MTCT was evaluated during a one-year follow-up period after birth.

Results: 290 pregnant women (185 with TDF therapy and 105 with TAF therapy) and 296 newborns (190 in TDF group and 106 in TAF group) were included. Both TDF and TAF effectively deceased HBV DNA levels with no significant difference, and the MTCT rates in TDF group and TAF group were similarly low (1.08% vs. 0.95%, P > 0.05). Moreover, no congenital malformations or growth and developmental abnormalities in newborns were observed in either group. However, serum creatinine was significantly higher and eGFR decreased significantly when treated by TDF, whereas TAF showed no significant renal effects.

Conclusions: Both TAF and TDF are effective in preventing HBV MTCT, with comparable MTCT rates. However, TAF demonstrated superior renal safety, making it a preferable option for preventing HBV MTCT in treatment-naïve mothers.

Background: Long-term tenofovir disoproxil fumarate (TDF) administration has been associated with potential adverse effects on renal function. Pegylated interferon-α2 (PEG-IFN-α2) therapy in chronic hepatitis B (CHB) patients increased estimated glomerular filtration rate (eGFR). Thus, the aim of this study was to analyze the influence of PEG-IFN-α-2b add-on to on-going TDF therapy in renal function in CHB patients.

Methods: This was a retrospective observational study. Ninety-one CHB patients who were treated with TDF for more than 48 weeks, had hepatitis B surface antigen (HBsAg) < 1500 IU/mL, and were hepatitis B e antigen-negative were recruited. Sixty-seven patients continued TDF monotherapy, and twenty-four patients received PEG-IFN-α-2b add-on therapy. Renal function indices were collected at baseline, 12 weeks, 24 weeks, and 48 weeks post-therapy. A linear mixed effects model for repeated measures was employed to analyze the associations between baseline information and serum β2-microglobulin (β2-MG)/urine α1-microglobulin (α1-MG) changes.

Results: HBsAg clearance rate was higher in TDF + PEG-IFN group compared with TDF monotherapy group (20.83% vs. 0.00%). There were no significant changes in blood urea nitrogen (BUN), creatinine (Cr), or eGFR in TDF monotherapy group. BUN and Cr was down-regulated, while eGFR was up-regulated at 48 weeks in TDF + PEG-IFN group. In TDF monotherapy group, serum β2-MG was elevated at 12, 24, and 48 weeks, whereas no significant changes were observed in TDF + PEG-IFN group. Serum β2-MG was higher in TDF monotherapy group than in TDF + PEG-IFN group. Urine α1-MG was increased in both groups at 48 weeks. TDF monotherapy was positive predictor for serum β2-MG increase, while TDF + PEG-IFN therapy negatively affect serum β2-MG level. Both TDF-based therapeutic strategies were positive predictors for urine α1-MG elevation.

Conclusion: PEG-IFN-α-2b might exert a protective effect against TDF-induced glomerular injury in CHB patients.

Objective: To assess the diagnostic efficacy of serum heparin-binding protein (HBP) as a standalone biomarker and in combination panels for distinguishing early-stage bacterial from viral pneumonia, and to explore its prognostic value in predicting progression to severe pneumonia.

Methods: This retrospective cohort study enrolled 269 participants, including 166 bacterial pneumonia patients (BPG), 42 viral pneumonia patients (VPG), and 61 age-/sex-matched healthy controls (NCG). Serum concentrations of four inflammatory biomarkers-HBP, procalcitonin (PCT), serum amyloid A (SAA), and C-reactive protein (CRP)-were quantitatively analyzed in all participants using immunoturbidimetry assays. Comparative analysis of inflammatory marker levels among the three groups was conducted, and receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of these four inflammatory biomarkers for distinguishing bacterial from viral pneumonia. Patients were stratified into mild and severe pneumonia groups based on CURB-65 score, followed by binary logistic regression and forest plot analysis to identify factors associated with disease severity.

Results: Serum levels of HBP, SAA, and CRP were significantly elevated in both BPG and VPG compared with the NCG (P < 0.01). PCT concentrations showed marked elevation exclusively in bacterial pneumonia (P < 0.01), while remaining comparable to CPG in VPG (P = 0.47). The four inflammatory biomarkers demonstrated favorable diagnostic performance for differentiating both bacterial and viral pneumonia, with enhanced diagnostic accuracy observed in bacterial cases. Notably, HBP exhibited the most prominent discriminative capacity (optimal cutoff: 17.9 ng/mL; AUC: 0.93, 95% CI 0.89-0.97; sensitivity: 81.93%; specificity: 96.72%). The biomarker combination strategy integrating HBP with other three indicators significantly improved diagnostic efficacy. Multivariate binary logistic regression coupled with forest plot analysis identified serum HBP as an independent predictor of severe bacterial pneumonia.

Conclusions: HBP emerges as a dual-functional biomarker demonstrating diagnostic precision for early-stage bacterial pneumonia and prognostic capability for disease progression. Compared to a single biomarker, the combined detection of HBP, PCT, SAA and CRP is more valuable for diagnosing bacterial pneumonia.

Antiretroviral therapy (ART) is an intervention aimed at preventing the development and spread of HIV. The persistence of proviruses in the CD4 + memory T cells, which are transcriptionally inactive and other drug-resistant reservoirs, makes treatment of chronic HIV-1 infection through pharmacological means complex. The major measures to deal with the disease involve reactivating the inactive viruses then clearing them off by using virus-specific cytotoxic effect and also by host immune responses. Broadcast screening and mechanism-based techniques have revealed a huge number of medications that can reactivate latent infections. The review carried out relies on Cochrane Central Register of Controlled Trials (CENTRAL), PubMed (NCBI), Scopus (Elsevier), and Web of Science (Clarivate) databases. Some of the therapeutic alternatives mentioned are Shock and Kill, cytokines, chemokines, histone methyl transferase inhibitor, immunotherapy, protein kinase C activator, P-TEFb activator, and uncharacterized ones like vorinostat and disulfiram. These techniques have proven to be effective using models working with CD4 + T lymphocytes and dormant cell lines in HIV-1 infected patients. The given paper includes an in-depth evaluation of the existing situation in the field and its hardships.

Background: SAM and HD domain-containing deoxynucleoside triphosphate triphosphohydrolase protein 1 (SAMHD1) is an intracellular protein that regulates a stable deoxynucleoside triphosphates (dNTPs) for normal cellular function. Many studies have documented SAMHD1-mediated restriction of RNA retroviruses and different DNA viruses in non-dividing myeloid cells, where it acts to deplete cellular dNTP pools to inhibit replication of the viral genome. Less is currently known regarding its ability to restrict the replication of other RNA viruses in different cell types. In this study, we investigate the role of SAMHD1 in modulating the replication of RNA viruses associated with respiratory virus infection, with a particular focus on seasonal influenza A virus (IAV). Moreover, our studies have assessed the ability of SAMHD1 to modulate IAV replication in two key cell types associated with the pathogenesis of IAV, namely epithelial and macrophage-like cells.

Methods: qPCR was used to examine expression of endogenous SAMHD1 in response to IAV infection and/or treatment with recombinant type I interferon (IFN) in epithelial (A549) and macrophage-like (THP-1) cells. CRISPR/Cas9 knockout (KO) of endogenous SAMHD1 was performed to assess the role of SAMHD1 in modulating IAV replication in A549 cells or in differentiated (d)THP-1. IAV infection and replication were also assessed in A549 and dTHP-1 SAMHD1 KO cells with stable doxycycline (DOX)-induced expression of SAMHD1 or of phosphorylation mutants of SAMHD1.

Results: CRISPR/Cas9 KO of endogenous SAMHD1 in dTHP-1 or A549 cells did not enhance virus release following infection with seasonal IAV. Moreover, reconstitution of KO cells with DOX-inducible SAMHD1 did not restrict the growth of seasonal IAV in dTHP-1 or A549 cells, despite SAMHD1-mediated restriction of a DNA virus (HSV-1) in both cell types. In contrast to seasonal IAV, we also observed restriction of highly pathogenic avian influenza (HPAI) A(H5N1) IAV replication in dTHP-1 cells expressing DOX-inducible SAMHD1.

Conclusions: Together, these studies indicate that neither endogenous nor DOX-inducible SAMHD1 restricts the growth of seasonal IAV in macrophage-like or epithelial cells.

This scoping review examines the neurological effects of maternal flavivirus infection, specifically Zika virus (ZIKV), Dengue virus (DENV), and Yellow Fever virus (YFV), on fetal brain development. Inclusion criteria focused on studies involving maternal infection and neurodevelopmental outcomes in offspring up to five years of age. The review found that ZIKV, especially the African Strain, exhibited neuroviolence and pronounced fetal brain abnormalities. Despite the presence of transplacental maternal transfer, these antibodies did not fully prevent congenital malformations, including microcephaly and developmental delays. Diagnostic limitations, such as serological cross-reactivity, particularly in regions where multiple flaviviruses co-circulate, were shown to impede effective clinical management. Additionally, the review highlights stark disparities in health infrastructure and prenatal care in Latin America, where the burden of Congenital Zika Syndrome (CZS) is disproportionately high. Findings emphasize the need for strain-specific diagnostics and therapeutics, along with long-term cohort studies that integrate virological, immunological, and socio-environmental perspectives. Ultimately, this review underscores the urgent need for equitable public health strategies and continued interdisciplinary research to address the teratogenic risks associated with maternal flavivirus infections.