Journal of Medical Virology最新文献

Hepatitis A is the most common form of acute viral hepatitis, and its control is critical to achieving the 2030 viral hepatitis elimination target. We conducted a comprehensive assessment of hepatitis A incidence across 204 countries and regions from 1990 to 2021. Annual incident cases and age-standardized incidence rates (ASIR) of hepatitis A were obtained from the Global Burden of Disease (GBD) study 2021. Joinpoint regression analysis evaluated long-term trends in ASIR, while Age-Period-Cohort (APC) analysis assessed the independent effects of age, period, and cohort. Decomposition analysis determined the drivers behind temporal changes in disease incidence. The Slope Index of Inequality (SII) and Concentration Index (CI) were employed to quantify cross-national inequalities in incidence. From 1990 to 2021, global hepatitis A cases declined by 7.25%, with age-standardized incidence rates (ASIR) demonstrating a universal downward trend. The most substantial ASIR reductions occurred in low-middle socio-demographic index (SDI) quintiles, whereas low-SDI quintiles showed paradoxical ASIR declines (AAPC: -1.56 95% CI: -1.71 to -1.40) alongside a 39.44% (95%UI: 28.04 to 50.48) case surge. Cases remained concentrated in children under 5. The age-period-cohort analysis confirmed highest risk in young children, with period and cohort risks declining over time. Decomposition analysis identified population growth as the primary driver of case increases. Health inequality analysis showed persistent absolute disparities despite relative improvements. Although global hepatitis A incidence has declined over three decades, trends are highly heterogeneous and significant inequalities persist. Achieving equitable burden reduction requires differentiated strategies and enhanced international collaboration, particularly for low-resource settings.

The C19-YRS was the first condition-specific for long COVID/post-COVID syndrome. Although the original C19-YRS evolved to the modified version (C19-YRSm) based on psychometric evidence, clinical content relevance, as well as feedback from patients and healthcare professionals, it has not been validated through Rasch analysis. The study aim was to psychometrically assess and validate the C19-YRSm using newly collected data from a large-scale, multicenter study (LOCOMOTION). In total, 1278 patients (67% Female; mean age = 48.6, SD 12.7) digitally completed the C19-YRSm. The psychometric properties of the C19-YRSm Symptom Severity (SS) and Functional Disability (FD) subscales were assessed using a Rasch Measurement Theory framework, assessing for individual item model fit, targeting, internal consistency reliability, unidimensionality, local dependency (LD), response category functioning and differential item functioning (DIF) by age group, sex and ethnicity. Rasch analysis revealed robust psychometric properties of both subscales, with each demonstrating unidimensionality, appropriate response category structuring, no floor or ceiling effects, and minimal LD and DIF. Both subscales also displayed good targeting and reliability (SS: Person Separation Index (PSI) = 0.81, Cronbach's α = 0.82; FD: PSI = 0.76, Cronbach's α = 0.81). Although some minor anomalies are apparent, the modifications to the original C19-YRS have strengthened its measurement characteristics and its clinical and conceptual relevance. Trial Registration: NCT05057260, ISRCTN15022307.

Tenofovir alafenamide (TAF) exhibits antiviral efficacy comparable to tenofovir disoproxil fumarate (TDF). Nonetheless, concerns persist regarding TAF's impact on the lipid profile and potential atherosclerotic cardiovascular disease (ASCVD) risk. This study evaluated long-term ASCVD risk in patients with chronic hepatitis B (CHB) treated with TAF or TDF using Korean National Health Insurance Service claims data. We retrospectively analyzed treatment-naïve patients with CHB who received TAF or TDF between 2017 and 2022. Cumulative ASCVD incidence was estimated using the Kaplan-Meier method and compared using the log-rank test. Propensity score (PS) matching and Cox regression were used to minimize confounding and identify ASCVD risk factors, respectively. Among 44,714 patients with CHB, 16,120 (36.1%) received TAF, whereas 28,594 (63.9%) received TDF. Over a median follow-up period of 3.0 years, ASCVD occurred in 817 patients (630 TDF-treated and 187 TAF-treated), with an annual incidence of 6.18/1000 patient-years (PYs). TAF was associated with lower ASCVD risk than TDF (4.60 vs. 6.88/1000 PYs; p < 0.001), a trend maintained after PS matching (4.67 vs. 6.67/1000 PYs; hazard ratio 0.70; p < 0.001) among 15,169 matched pairs. Older age, male sex, hypertension, current smoking, and aspartate aminotransferase ≥ 40 U/L were risk factors for ASCVD development. Despite concerns about lipid metabolism, TAF did not increase ASCVD risk compared with TDF, offering reassurance for clinicians selecting antiviral therapies for patients with CHB.

Zika virus (ZIKV) infection is known to cause microcephaly in newborns, and its outbreaks have previously emerged as a global public health crisis. The lack of a preventive vaccine or specific antiviral drugs underscores the urgency of investigating the detailed mechanisms of pathogenesis. We identified that interferon-induced protein 44 (IFI44) is significantly upregulated following ZIKV infection, but its role in ZIKV pathogenesis remains unclear. Using A549 and 2FTGH cells, we established ZIKV-infected cell models and employed quantitative real-time PCR and Western blotting to demonstrate that IFI44 overexpression suppressed ZIKV replication, whereas IFI44 knockdown via specific small interfering RNA promoted viral replication. Mechanistically, IFI44 inhibited early-stage ZIKV infection, including viral attachment and entry into host cells. Further analyses revealed that IFI44 promoted IFN-β expression, triggering activation of the Jak/STAT signaling pathway-as evidenced by increased phosphorylated STAT1 (p-STAT1), enhanced interferon-stimulated response element activity, and upregulated the downstream interferon-stimulated genes (MX1, OAS2, IFIT2, and RIG-I). Collectively, these findings demonstrate that ZIKV infection induced IFI44 expression, which acts as a positive feedback regulator of the Jak/STAT pathway to restrict viral replication. Our results establish IFI44 as a key component of the host antiviral response against ZIKV, highlighting its potential as a therapeutic target.

Early detection of human papillomavirus type 16 (HPV16), the primary etiological agent of cervical cancer, is essential for effective clinical management. Specifically, detecting HPV16 E7 mRNA expression provides superior prognostic value, identifying transcriptionally active infections most likely to progress to precancerous lesions. In this study, we developed a fluorescence-based nanobiosensor that integrates catalytic hairpin assembly (CHA) with Fe₃O₄@Au core-shell nanoparticles (Fe₃O₄@Au NPs). This novel design combines magnetic enrichment and enzyme-free signal amplification, distinguishing it from prior HPV biosensors by enabling ultrasensitive detection in complex matrices like first-void urine (FVU). The biosensor showed linear fluorescence responses from 0.002 to 1 pM in PBS and 0.1-1 pM in FVU, with excellent specificity for single-base mismatch discrimination. It remained stable for 45 days. Validation using RNA from HPV16 plasmid-transformed E. coli and CaSki cells confirmed robust performance, while clinical swab specimens matched commercial assays completely. This biosensor offers a promising tool for early HPV16 detection in screening programs.

Non-hepatotropic viruses (NHVs), as a category of pathogens not primarily targeting the liver, can also cause hepatic injury. Liver injury associated with Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, in particular, often attracts significant clinical attention. This retrospective cohort study analyzed the seroprevalence and clinical features of EBV and CMV infections among patients in Beijing from 2020 to 2024, with a focus on the impact of immunosuppression status on liver injury patterns. The CMV IgM positivity rate was 4.00% (646/16,201), and the EBV IgM positivity rate was 7.84% (1007/12,838), both showing significant upward annual trends (p < 0.001). Analysis of 236 IgM-positive inpatients revealed a "bifurcation phenomenon": the non-immunosuppressed group exhibited more severe hepatocellular injury (e.g., ALT levels 6.5- to 10.9-fold higher) and cholestatic damage (e.g., CMV group: TBIL increased 7.8-fold), yet had better clinical outcomes (adverse outcome rate: 0-4.8%) compared to the immunosuppressed group (adverse outcome rate: 18.4-27.8%, p < 0.05). Further analysis of 125 patients with confirmed liver injury demonstrated that the immunosuppressed group had severe CD4 + T-cell depletion and inverted CD4 + /CD8+ ratios. During EBV and CMV co-infection, the immunosuppressed group showed higher CMV DNA detection rates (66.7% vs. 20.0%, p = 0.0097) and viral loads (median 2675 vs. 625 copies/mL, p = 0.002). Within the immunosuppressed group, patients with CD4 + T-cell counts > 300 cells/μL had higher ALT and AST levels, supporting an immune-mediated injury mechanism. These findings indicate that immune status and virus type jointly shape the clinical spectrum of EBV/CMV-related liver injury. The dissociation between severe liver injury and favorable prognosis in non-immunosuppressed patients underscores the role of immune pathology, while poorer outcomes in immunosuppressed patients are driven by CD4 + T-cell depletion, impaired viral clearance, and extrahepatic complications.

Human metapneumovirus (hMPV) causes mild and self-limiting disease in adults. However, the risk factors for serious adverse outcomes following hMPV infection in adult patients without preexisting chronic airway diseases remain poorly understood. We conducted a territory-wide retrospective study on adult patients (aged ≥ 18 years) without chronic airway diseases hospitalized for hMPV infections between January 1, 2016 and June 30, 2023 in Hong Kong. We assessed the incidence and risk factors for in-patient mortality, severe respiratory failure (SRF), secondary bacterial pneumonia and acute kidney injury (AKI) were assessed. A total of 1552 eligible adult patients without chronic airway diseases hospitalized for hMPV infections were analyzed. Within the index admission, 92 (5.9%) patients died. Ischemic heart disease (IHD) was associated with increased risks of SRF [adjusted odds ratio (aOR) 2.00 (95% CI 1.48-2.71), p < 0.001]. IHD, heart failure (HF), and history of ischemic stroke were significant predictors for AKI [aOR 1.51 (95% CI 1.12-2.04), 2.87 (95% CI 2.14-3.85), and 1.47 (95% CI = 1.12-1.93), p = 0.007, < 0.001, and 0.005, respectively). Patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) were at increased risk of in-patient mortality [aOR 6.36 (95% CI 2.34-17.26), p < 0.001] and SRF [aOR 8.80 (95% CI 3.84-20.16), p < 0.001]. The presence of cardiovascular diseases and ESKD requiring RRT is a strong predictor of severe in-hospital outcomes among adult patients without chronic airway diseases who are hospitalized for hMPV infections.