Journal of Medical Virology最新文献

Herpes simplex virus (HSV) infections impose a substantial global health burden, yet regional, subtype-specific epidemiology in dermatology settings remains underexplored. We analyzed laboratory-confirmed HSV tests (PCR, viral culture and IgG ELISA) performed at the Dermatology Hospital of Southern Medical University from 2019 to 2024 to characterize subtype distribution, demographics, anatomical sites, temporal trends and diagnostic performance. Overall, HSV was detected in 32.84% of patients, with HSV-2 significantly more prevalent than HSV-1 (22.83% vs 10.02%, p < 0.0001). Over time, HSV-1 increased (23.55% to 34.65%, p = 0.0060) while HSV-2 declined. HSV-1 was more common in females than males (14.26% vs 7.57%, p < 0.0001) and in children (highest in ages 0-9 years: 24.71%), whereas HSV-2 peaked in adults (ages 40-49 years: 29.3%). Anatomically, HSV-1 infections were predominantly oral/cephalic, while HSV-2 occurred mainly in anogenital sites (89.94%). Viral culture showed high specificity (99.83%) but lower sensitivity (64.52%) relative to PCR, supporting PCR as the preferred diagnostic method. Latent infections (47.44%) confirmed HSV's lifelong persistence. These findings indicate current dominance of HSV-2 alongside a rising burden of HSV-1, with distinct demographic and anatomical patterns, and underscore the need for multicenter data to refine regional epidemiology and inform targeted prevention strategies.

The current highly active antiretroviral therapy (HAART or ART) effectively suppresses de novo HIV-1 infection but fails to eliminate HIV reservoir cells, which leads to rapid viral rebound upon ART cessation. Chimeric antigen receptor (CAR) T cells engineered to target HIV-1 Env⁺ cells offer a promising strategy to eliminate or control these persistent reservoirs and achieve durable control of HIV-1 infection. However, a major challenge is the susceptibility of such CAR-T cells to HIV infection, especially those soluble CD4 (sCD4)-based CAR-T cells. In this study, an sCD4-based CAR incorporating the S85C mutation in the CD4 Ig-like domain 1 (termed D1C) was engineered to enable disulfide bond formation with the HIV-1 envelope glycoprotein (Env), thereby reducing viral entry and conferring protection against HIV infection. D1C/sCD4 CAR-T cells exhibited enhanced T-cell activation and cytotoxicity in response to Env stimulation while demonstrating resistance HIV-1 infection in vitro and in vivo. Furthermore, the herpesvirus entry mediator (HVEM) intracellular domain was identified as an optimal costimulatory domain, enhancing cytokine induction, cytotoxicity, and promoting a favorable central memory phenotype and persistence of CAR-T cells. In humanized mouse models, D1C/sCD4 CAR-T cells demonstrated superior persistence and improved control of HIV rebound following ART interruption compared to wild-type (WT)/sCD4 CAR-T cells. These findings highlight a novel strategy to enhance the efficacy and durability of HIV-targeted CAR-T cell therapy by combining HIV resistance and optimized co-stimulation.

The coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) is an uncommon but clinically important serological pattern, with a reported prevalence ranging from 2.8% to 35.95%. This study aimed to evaluate the authenticity of this coexistence pattern and to investigate its underlying causes. A total of 300 sera co-positive for HBsAg and anti-HBs were incubated with recombinant HBsAg (rHBsAg) of the adw, adr, and ayw serotypes, as well as with pooled clinical HBsAg-positive sera, to calculate the neutralization index (NI) of anti-HBs. In parallel, the same co-positive samples were incubated with pooled clinical anti-HBs-positive sera to determine the NI of HBsAg. Additionally, 180 sera from healthy individuals under 32 years of age with isolated anti-HBs positivity were tested against adw and adr rHBsAg and pooled clinical HBsAg-positive sera to establish neutralization thresholds. Among the 300 co-positive samples, HBsAg was confirmed positive in 100%, and anti-HBs was confirmed positive in 89.00% (267/300). The prevalence of true coexistence decreased with increasing anti-HBs concentrations: 91.55% in the 10.00-50.00 mIU/mL group, 86.11% in the 50.00-100.00 mIU/mL group, and 76.92% in the > 100.00 mIU/mL group (p = 0.025). In serotype analysis, 46.82% (125/267) of anti-HBs were neutralized by adw and adr rHBsAg but not by ayw rHBsAg. Another 49.44% (132/267) could not be neutralized by any of the three rHBsAg preparations but were neutralized by pooled clinical sera. The proportion of truly anti-HBs positive individuals was relatively high among co-positive samples, and this proportion increased as anti-HBs concentrations decreased. The coexistence of HBsAg and anti-HBs may be attributed to coinfection with both ayr and common serotypes, or to post-vaccination infection with ayw or ayr serotypes.

The risk of developing hepatocellular carcinoma (HCC) persists in patients with cirrhosis and a sustained virologic response (SVR, the eradication of hepatitis C virus [HCV]), and therefore surveillance for HCC is recommended. However, patients with mild or no fibrosis are usually at low risk and HCC surveillance is not recommended in many guidelines. Nevertheless, some patients experience post-SVR HCC despite having low degree liver fibrosis. We characterized the changes in liver fibrosis in patients in whom HCC developed after SVR. We performed a nationwide multicenter study, during which HCC developed in 332 of 6047 patients (5.5%) with no history of HCC who achieved SVR. FIB-4 index, the laboratory index of liver fibrosis, was calculated at the start of anti-HCV therapy and at a diagnosis of HCC, and the changes were characterized. Most patients who developed HCC after SVR had cirrhosis or advanced liver fibrosis (FIB-4 index > 3.25) before anti-HCV therapy, including some whose liver fibrosis regressed after SVR. Some patients (3.6%) without substantial fibrosis (FIB-4 index ≤ 3.25) before anti-HCV therapy developed HCC with the progression of liver fibrosis after SVR. Finally, 5 patients (1.6%) had mild or no fibrosis (FIB-4 index < 1.45) both before anti-HCV therapy and when HCC developed. Most HCCs in patients who achieve SVR develop in association with liver cirrhosis or advanced fibrosis, but some develop in livers without substantial fibrosis. In addition, post-SVR HCC can develop in patients with mild or no fibrosis both before anti-HCV therapy and after SVR.

Cytomegalovirus (CMV) infections remain a major complication following allogeneic hematopoietic stem cell transplantation (allo-HCT), with refractory infections associated with increased morbidity and mortality. Machine learning (ML) approaches may improve risk stratification and clinical management of CMV infections. This retrospective multicenter study analyzed 933 allo-HCT recipients from 21 Spanish centers (2014-2018) using data from the Spanish Hematopoietic Transplantation and Cell Therapy Group registry. Three ML models were developed to predict: (1) CMV DNAemia occurrence, (2) clinically significant CMV infection (csCMV-I), and (3) refractory CMV infection (CMV-R). Six supervised ML algorithms were evaluated using 25 repeated fivefold stratified cross-validation, including Random Forest, Support Vector Machine, Decision Trees, XGBoost, Elastic Net, and PLS-Logistic Regression. CMV DNAemia occurred in 493 recipients (53%), with 356 (72%) developing CsCMV-I and 91 (26%) progressing to CMV-R. The optimal models achieved: XGBoost for CMV DNAemia and CsCMV-I prediction (sensitivity 0.97) and SVM for CMV-R prediction (sensitivity 0.58). Key predictive features included recipient CMV serostatus, conditioning regimens, GvHD occurrence, recipient characteristics, and immunosuppressive protocols, with distinct signatures for each outcome. ML models successfully identified distinct clinical profiles associated with different CMV outcomes in allo-HCT recipients, achieving high sensitivity but moderate discriminatory capacity (AUC 0.55-0.67). Despite limitations including pre-letermovir era data, this work establishes a foundation for precision risk stratification as a complement to-not replacement for-current prophylaxis strategies. Prospective validation in contemporary cohorts is needed before clinical implementation.

Hepatitis E virus (HEV) is an emerging transfusion-transmissible pathogen, yet epidemiological data from the Middle East remain limited, and differences in serological assay performance complicate interpretation of seroprevalence. Lebanon lacks national HEV surveillance data and has no blood donor screening policy. In this cross-sectional national study, 3000 blood donors from all Lebanese governorates (July 2023-August 2024) were screened for anti-HEV IgG and IgM using two commercial platforms: Euroimmun ELISA and Roche Elecsys electrochemiluminescence immunoassay (ECLIA). This study represents the first large-scale, peer-reviewed evaluation of the Roche Elecsys Anti-HEV assays in a national blood donor population. All samples that were positive or borderline by either serological assay were tested for HEV RNA using real-time RT-PCR (Altona RealStar® and Roche Cobas®). Anti-HEV IgG seroprevalence differed significantly between assays (Euroimmun: 1.13% vs. Roche Elecsys: 1.93%; p < 0.001). IgM prevalence was 0.07% and 0.33%, respectively. Overall agreement between assays was high (IgG: 98.7%; IgM: 99.7%), although Cohen's κ indicated limited concordance, with Roche Elecsys identifying additional low-reactivity seropositive donors. Seropositivity varied across regions, with higher rates observed in South Lebanon (4.0%) and North Lebanon (3.1%). HEV RNA was not detected in any tested donor. HEV exposure among Lebanese blood donors is low but geographically distributed. Seroprevalence estimates were strongly assay-dependent, indicating that HEV burden may be underestimated when lower-sensitivity platforms are used. These findings highlight the importance of assay selection in HEV epidemiological studies and support consideration of selective HEV nucleic acid testing for high-risk recipients to inform evidence-based blood safety policy in Lebanon.

A significant numerical increase of genotype GII.17 norovirus-associated sporadic infections was observed in multiple cities in China during the 2024-2025 season. We collected fecal samples from hospitalized children with acute gastroenteritis from 29 sentinel hospitals nationwide to screen for norovirus. A total of 18.7% (n = 412) of the samples tested positive, with a decrease in genotype GII.4 (27% of all positive cases) coinciding with an increase in GII.17 (62%). Comparative phylogenetic analysis of RNA-dependent RNA polymerase and capsid gene sequences revealed that these GII.17[P17] strains were most closely related to strains circulating in the United States and European countries during 2023-2024, with which they shared a recent common ancestor. The evolving epidemiology of norovirus, characterized by the circulation of multiple genotypes, highlights the need for ongoing surveillance and research to better understand its impact and guide the development of vaccines.

Chronic hepatitis B virus (HBV) infection poses a significant global health burden, with long-term antiviral therapy being the primary treatment. However, predicting disease progression and the risk of viral relapse after treatment cessation remains difficult. Serum HBV pregenomic RNA (pgRNA) has recently gained attention as a potential biomarker reflecting intrahepatic viral activity, particularly that of covalently closed circular DNA (cccDNA). This study aimed to evaluate pgRNA's clinical utility as a prognostic marker in chronic HBV (CHB) patients on long-term therapy. A systematic literature review was conducted using PubMed and Scopus, including studies up to August 27, 2024. Selected studies assessed pgRNA in relation to disease prognosis, treatment response, and relapse. Meta-analysis showed a significant reduction in pgRNA levels post-treatment (mean difference: 1.64; 95% CI: 0.79-2.49), consistent with decreases in HBV DNA and HBsAg. These findings support pgRNA may serve as a promising surrogate marker for treatment prognosis and potential viral relapse in HBV patients.

Human Parechovirus A (PeV-A) is a virus with near-universal infection by age five; however, neonatal infections can lead to meningoencephalitis, sepsis, and death. Prior to the COVID-19 pandemic, PeV-A showed biennial seasonality with late summer peaks, but multiple viruses have had shifted circulation post-pandemic. PeV-A is not universally included in neonatal sepsis testing; thus, the frequency and clinical spectrum of PeV-A neonatal meningoencephalitis are not fully described. We sought to evaluate the epidemiology, seasonality, and clinical presentation of neonatal PeV-A in the 2024 season. We collected remnant cerebrospinal fluid samples from febrile infants under 60 days at a single children's hospital in Southwestern Pennsylvania and assessed for PeV-A and enterovirus (EV). Six out of 107 (5.6%) febrile infants were positive for PeV-A and 24 (22.4%) were positive for EV. PeV-A infections occurred from June to September. PeV-A positive patients had a distinct combination of higher maximum temperature, rash, and leukopenia without pleocytosis. None of these infants had severe disease. Systematic surveillance of PeV-A is required to completely understand ongoing PeV-A circulation patterns, expected clinical course, and long-term developmental implications.