Journal of Medical Virology最新文献

Comparative transcriptome analyses of gamma herpesviruses have been revolutionized by long-read sequencing and integrative multi-omics approaches, enabling unprecedented resolution of viral gene expression. Cross-species studies of Kaposi's sarcoma-associated herpesvirus (KSHV), Epstein–Barr virus (EBV), and murine gamma herpesvirus 68 (MHV68) have uncovered a vast diversity of transcript isoforms, including alternative 5′/3′ UTR variants, alternative splice isoforms, and transcripts encoding truncated or extended coding sequences. These efforts revealed novel transcript isoforms harboring partial open reading frames, entirely new ORFs, and an expanding repertoire of viral non-coding RNAs. Additional regulatory mechanisms, such as promoter dependence on viral replication factors, selective polyadenylation site usage, frameshifting via alternative splicing, and extensive readthrough transcription, further illustrate the complex strategies governing gamma herpesvirus transcriptomes. This review synthesizes these discoveries, highlighting transcriptional strategies employed by gamma herpesviruses for persistence through different phases of replication, while outlining how integrative transcriptomics has reshaped our understanding of herpesvirus gene regulation.

Dengue poses a significant arboviral threat in Brazil, with 2024 recording the largest outbreak to date. This prospective observational study was conducted during the 2024 outbreak with unvaccinated patients at Eduardo de Menezes Hospital, Belo Horizonte. A total of 556 patients were included, of whom 169 had complete clinical and laboratory data. Patients with suspected dengue underwent clinical and hematological evaluations, as well as diagnosis by RT-qPCR, and ELISA. These parameters were employed to assess the relationship between diagnostic methods, hematological changes, and disease severity. RT-qPCR confirmed dengue infection in 60% of with clinical symptoms, with partial overlap between PCR positivity and IgM detection, reflecting time-dependent diagnostic windows. High IgG seropositivity indicated widespread prior exposure in the population. Thrombocytopenia was the most consistent hematological finding, with platelet counts declining until day 8 of symptoms and recovering around day 10; a secondary decline was observed in some patients with prolonged hospitalization. No significant differences in clinical severity were observed across serotypes, although DENV-2 showed a trend toward lower platelet counts. These findings highlight the importance of integrating molecular and serological diagnostics during outbreaks and reinforce platelet monitoring as a key parameter for identifying patients at risk of severe dengue.

Neutralizing emerging SARS-CoV-2 variants requires antibodies effective not only against epitope mutations but also under variable antigenic presentations. We assessed the neutralization capacity of the same anti-RBD monoclonal antibody (8A5) expressed as IgG, IgA, or IgM against 18 variants, identifying three neutralization classes: variants susceptible to all isotypes, variants resistant to IgG but sensitive to IgA/IgM, and variants resistant to all isotypes. Mutation analysis revealed that S371L-S373P-S375F disrupted IgG binding while partially preserving IgA/IgM activity, whereas L371F induced conformational changes abolishing all antibody interactions. Notably, some variants lacking these mutations still escaped IgG, suggesting geometric factors contribute to differential efficacy. To explore this, we performed negative-stain electron microscopy, which showed heterogeneous spike distributions across virion surfaces. ELISA assays with decreasing spike concentrations revealed that IgG binding declined sharply under low antigen density, while IgA and IgM maintained strong binding, reflecting their extended architecture and multivalency. These findings indicate that spatial adaptability, in addition to affinity, contributes to effective neutralization. IgA and IgM can engage antigens under sparse or conformationally altered conditions, suggesting potential advantages over IgG against certain variants. These insights may support the rational design of IgA- and IgM-based antibody therapeutics, highlighting their potential role in combating SARS-CoV-2 variants and other emerging viral pathogens.

Melatonin has demonstrated antioxidant, anti-inflammatory, and potential antiviral properties. Its therapeutic role in critically ill COVID-19 patients admitted to intensive care was underexplored at the start of the pandemic. We conducted a quasi-experimental, pragmatic study over 4 consecutive uninterrupted time periods alternating control groups receiving standard of care (SoC) with treatment groups receiving SoC plus high-dose oral bedtime melatonin (50–200 mg) (OBM). The primary endpoint was 90-day mortality; secondary outcomes included sequential organ failure assessment (SOFA) scores at 4, 7, 14, and 30 days and pre-defined severe adverse events (SAEs). A total of 335 of 339 consecutive patients with a predicted stay > 48 h were enrolled; 202 received OBM with SoC and 133 received SoC alone. OBM was dispensed during the second (n = 162) and fourth (n = 40) study periods after the first (n = 40) and third (n = 93) control group periods, respectively. Melatonin therapy was associated with significantly lower 90-day mortality (20.8% vs. 36.1%, OR 0.46, 95% CI 0.28–0.76). Subjects receiving melatonin had lower SOFA scores on Day 4 and subsequent study visits. SAEs occurred in 84 (41.6%) subjects on OBM and in 80 (60.2%) receiving SoC (risk ratio 0.68, 95% CI 0.54–0.87; p = 0.001). High-dose oral melatonin was safe and associated with improved clinical outcomes. Further evaluation of melatonin and its potential antiviral effects in future epidemics is warranted.

To compare the repertoire of anti-beta-Coronavirus antibodies detected in dental pulp samples (systemic immunity) collected from individuals from the early 19th century previously investigated for dental calculus (local immunity) serological response, We investigated 10 dental pulp samples collected from 10 individuals excavated from a 1810–1813 military site in Charleville-Mézières, France. The samples had previously been investigated for dental calculus serology. Dental pulp serology performed under a mini-blot format, incorporated one positive and one negative control, and conjugated antibodies against the five classes of immunoglobulins. Dental pulp IgE serological response reliability was assessed by in silico analyses. Controls yielded expected results. Anti-Coronavirus antibodies were detected in three individuals, comprising anti-beta Coronavirus IgE in three individuals, IgG in two individuals, and IgA in one individual. IgA and IgG anti-alpha Coronavirus were each detected in one individual. These results agreed with those previously obtained from the same 10 individuals with anti-beta-Coronavirus pooled IgG/IgA/IgM dental calculus paleoserology. Dental pulp paleoserology confirmed Coronavirus exposure in three individuals from the start of the 19th century in France. Translating these data into the modern medical literature, we propose that two centuries ago, some individuals suffered a yet unidentified beta-Coronavirus infection.