Journal of Medical Virology最新文献

To evaluate the durability of long-acting cabotegravir (CAB) plus rilpivirine (RPV), available in Italy since June 2022, for maintaining HIV-1 virological suppression. This multicentric observational study included 191 virologically suppressed adults (HIV-RNA < 50 copies/mL) from 11 centers in Tuscany, followed from first CAB + RPV injection until discontinuation, death, or last visit. Discontinuation was defined as regimen switch or two consecutive missed doses, virological failure (VF) as two consecutive HIV-RNA > 50 copies/mL or a single > 1000 copies/mL. Kaplan–Meier survival analysis assessed discontinuation rates. Follow-up was 209.5 person-years with a median of 1 year (IQR 0.5–1.5). Median age was 51 years (IQR 43–58); 81.7% were male; median ART duration was 13.8 years (IQR 8.7–20.2). Eighteen participants (9.2%) discontinued due to adverse events (3.7%), VF (2.6%), personal choice (2.1%), medical decision (0.5%), or loss to follow-up (0.5%). Overall discontinuation was 8.5/100 person-years (95% CI: 5.4–13.6). VF incidence was 2.3/100 person-years (95% CI 0.9–5.7). All VFs, occurred within 28 weeks, except one at Week 72 with resistance mutations. Discontinuation rates were slightly higher than clinical trials but consistent with real-world data. The VF incidence was slightly higher than reported in prior reports, highlighting the need for real-life clinical monitoring.

Epstein-Barr virus (EBV) is a member of the gamma-herpesvirus subfamily that is prevalent in the human population. There are two phases of EBV infection: latent infection and lytic infection. During lytic reactivation, host innate immune responses are activated to restrict EBV replication. Here, we identified ETS translocation variant 5 (ETV5) as a negative regulator of innate immune responses to facilitate EBV reactivation. ETV5 expression was upregulated by the EBNA1/BRD7 axis, which had been previously described by us, during EBV latent infection. When EBV was induced into lytic replication, the expression of ETV5 was further increased, and ETV5 overexpression dramatically enhanced the lytic replication of EBV. Mechanistically, upon EBV reactivation, the overexpression of ETV5 suppressed the activation of TANK-binding kinase 1 and interferon regulatory factor 3 (IRF3), as well as the transcription of interferon beta (IFNB1) gene and interferon-stimulated genes (ISGs). The effect of ETV5 knockdown could be reversed by an inhibitor of innate immunity pathway. These findings position ETV5 as a critical accelerator of EBV reactivation through immune evasion, revealing new therapeutic targets for managing EBV-associated diseases.

Herpes simplex virus type 1 (HSV-1) is among the most common pathogens in the human population. Primary infection and reactivation of the virus can cause serious diseases and death. The drug resistance to all approved anti-HSV agents poses a significant challenge, especially for immunocompromised patients. This study focuses on some details of the dimeric bisbenzimidazole DB₂A(7) synthesis and its antiviral properties of against both HSV-1 sensitive and resistant acyclovir isolates. Optimization of the synthesis of DB₂A(7) resulted in an increase in the total yield from 20% to 44%, reduction of labor intensity and removal of highly toxic and carcinogenic hydrazine. The DB₂A(7) binding to thymus DNA was confirmed by a combination of physicochemical methods including calculation of the binding constant. DB₂A(7) demonstrated the in vitro capacity to inhibit viral activity, both before and after cell infection, and effectively inactivated cell-free viruses. Gene expression analysis by RT-PCR revealed a significant reduction in the transcription of the gene encoding the immediate early ICP0 HSV-1 protein, suggesting a mechanism of action different from that of acyclovir. We first demonstrated the in vivo preventive effect of DB₂A(7) towards lethal skin HSV-1 infection in mice as well as its capacity to protect animals from lethal genital herpes. The data obtained implied the potential of the synthesized DB₂A(7) as a new antiviral agent against the lethal HSV-1 infection.

Epstein-Barr virus (EBV), a ubiquitous human γ-herpesvirus infecting over 90% of the global population, has been increasingly implicated as a key environmental trigger in the development of various autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA). EBV latent proteins (e.g., EBNA1, EBNA2, LMP1) mimic host antigens and dysregulate B and T cell responses, promoting autoreactivity. Novel therapeutics, including small-molecule latency disruptors, EBV-specific T cell therapies, and advanced B-cell depletion strategies, have shown promise in addressing EBV-driven autoimmunity. Understanding its pathogenic mechanisms and therapeutic implications is critical for improving disease management. This review summarises EBV's roles in autoimmunity through mechanisms including molecular mimicry, B-cell transformation, and immune dysregulation. It also examines emerging antiviral and immune-modulating strategies targeting EBV infection and latency.

At the end of 2024, human metapneumovirus (HMPV) infections surged significantly in China, attracting widespread attention and concerns at home and abroad. This study aims to investigate the prevalent and molecular characteristics of the HMPV infection in children during 2021–2025 in Shanghai, China, including the latest epidemic prevailing in December 2024. The demographic information and the results of laboratory pathogen detection from July 2021 to May 2025 were collected and analyzed. The G gene of HMPV was amplified and sequenced using Sanger sequencing, followed by phylogenetic analysis to determine the genotypes. A total of 26 952 pediatric patients with acute respiratory tract infection (ARTI) were enrolled in this study. The overall positive rate of HMPV was 4.65% (1252/26952). The popularity mainly peaked in Winter and early Spring, with the highest detection rate in 1~3 years age group and with no statistically significant gender difference. Among 206 successfully sequenced G gene samples, four genotypes were identified: A2c (66.99%, 138/206, all of which were the A2c_111nt-dup variant), B2 (24.76%, 51/206), A2b (7.77%, 16/206), and B1 (0.49%, 1/206). From 2021 to 2024, the A2c_111nt-dup variant was dominant. However, a genotype shift to B2 occurred in December 2024, leading to a significant surge in HMPV infections that persisted into 2025. The dominant genotype of HMPV has changed from A2c_111nt-dup to B2, causing the outbreak in Shanghai from December 2024 to April 2025. Sustained surveillance is essential for predicting and monitoring its prevalence.

This multicenter clinical study evaluated 17 common pathogens in 1922 pharyngeal swab samples, comparing the diagnostic performance of polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) with that of clinically routine quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The results were validated using Sanger sequencing as the gold standard. Our results showed that among the samples with single-pathogen infections (1037 cases, 53.95%), the three most frequently detected pathogen were influenza A virus (IAV) (296 cases, 15.40%), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (164 cases, 8.53%), and Mycoplasma pneumoniae (94 cases, 4.89%). Similarly, among the samples with co-infections of two or more pathogens (382 cases, 19.88%), the three most frequently detected pathogens were IAV (148 cases, 7.70%), SARS-CoV-2 (107 cases, 5.57%), and M. pneumoniae (67 cases, 3.49%). In the comprehensive evaluation of 17 respiratory pathogens, PCR-QDFA demonstrated comparable diagnostic performance to qRT-PCR, with an overall sensitivity of 99.78% (99.44%–99.92%) (vs. qRT-PCR: 99.82% [99.48%–99.94%]) and specificity of 99.94% (99.90%–99.96%) (vs. qRT-PCR: 99.95% [99.91%–99.97%]). PCR-QDFA offers significant operational advantages, including high-throughput capacity (96 samples per run) and lower cost.

The detection of neutralizing antibodies (NAbs) is crucial for evaluating immune protection against viral infections. This study assessed two ELISA-based surrogate virus neutralization tests (sVNTs): the novel GeneTex U-OK SARS-CoV-2 Neutralizing Antibody Detection ELISA kit and the FDA-authorized GenScript cPass SARS-CoV-2 Neutralization Antibody Detection kit. The GeneTex U-OK kit contains recombinant spike proteins from the wild-type strain and Omicron subvariants BA.1, BA.2, and BA.4/BA.5. A total of 115 serum samples were analyzed, including 75 from SARS-CoV-2 unvaccinated individuals and 40 from vaccinated individuals. No participant had evidence of prior SARS-CoV-2 infection, as confirmed by negative anti-nucleocapsid antibody tests. Compared with the GenScript cPass kit, the GeneTex U-OK kit demonstrated 100% positive agreement (95% CI: 90.4–100.0%) and 100% negative agreement (95% CI: 95.4–100.0%) in detecting NAbs against the wild-type strain, corresponding to 100% sensitivity and 100% specificity. When compared with viral neutralization assays, it achieved 100% concordance for Omicron BA.1, BA.2, and BA.4/BA.5 subvariants, with correlation coefficients (R) of 0.85, 0.98, and 0.46, respectively. These findings highlight the accuracy and reliability of the GeneTex U-OK kit, indicating its potential as a valuable tool for monitoring vaccine effectiveness and identifying individuals with protective NAbs against vaccinated individuals, including Omicron variants.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with unknown etiology and heterogeneous symptomology for which there are no validated tests for definitive diagnosis. We examined 873 longitudinal serum samples from ME/CFS patients (n = 40) and 378 from healthy control individuals (n = 16) for differences in human herpesvirus and endogenous retrovirus-K (HERV-K) dUTPase IgG antibodies by ELISA. The results of this study demonstrate a significant increase in dUTPase IgG antibodies to the herpesviruses Epstein-Barr virus (EBV), human herpesvirus-6 (HHV-6) and varicella zoster virus (VZV) in ME/CFS compared to healthy-controls (p < 0.001). Notably, 72.5% (n = 29) of ME/CFS patients simultaneously co-expressed antibodies to multiple herpesvirus and HERV-K dUTPases compared to 31% (n = 5) of the healthy controls. Chi-square test analysis showed strong associations for EBV, HHV-6 and VZV dUTPase antibodies seropositivity (p < 0.001) and Spearman correlation analysis revealed significant positive associations of EBV and HHV-6 dUTPase IgG antibodies with fatigue. Further examination of the distribution of dUTPase antibodies across fatigue severity groups show that heightened dUTPase IgG levels cluster with ME/CFS patients exhibiting moderate and severe fatigue. These findings highlight the importance of examining herpesvirus dUTPase IgG across severity groups in aiding with current challenges for stratifying ME/CFS patients due to the heterogeneity in symptomology.