Journal of Medical Virology最新文献

Human cytomegalovirus (HCMV)-associated ocular diseases have gained increasing attention due to a recent rise in cases diagnosed in Asia. A glycoprotein encoded by the virus UL55 gene, glycoprotein B (gB), is essential for viral entry and a primary target for naturally-produced antibodies and vaccine development. gB is classified into five genotypes (gB1–gB5) based on polymorphisms surrounding the furin cleavage site. This study analyzed the UL55 gene in 62 blood and ocular specimens of Japanese patients with CMV viremia and CMV-associated ocular diseases. Distinct gB genotype distributions were found between sample types (p = 0.008): gB2 was the most prevalent genotype in blood samples (41%, 11/27), while gB3 (43%, 15/35) and gB1 (37%, 13/35) predominated in ocular fluids. Viral loads were significantly higher in gB1 and gB3-positive samples compared with gB2 (p = 0.016). A shared gB1/gB3-specific peptide (aa 190–204; SRVIAGTVFVAYHRD), distinct from that of gB2, exhibited reduced HLA class II binding. In addition, a K518R substitution was identified in 80% of gB1 and gB3 variants in our cohort and other Asian-derived GenBank entries, but only 3% of European origin strains. This substitution was significantly enriched in ocular fluids from patients with CMV ocular infection (71%, 17/24), compared with blood from patients with CMV viremia (32%, 8/25) (p = 0.01). The predicted structural modeling infers that this substitution is located in the core of gB Domain III, and potentially increase the local molecular stability in this region. Evolutionary analyses indicated positive selective pressure at this site, implying the biological significance. These findings infer that genetic variations enriched in ocular fluids and Asian-derived HCMV strains, may contribute to ocular pathogenesis through influencing on viral entry and reduced immune recognition.

Respiratory viral infections (RVIs) are a major cause of global morbidity and mortality. Severe cases are driven by dysregulated inflammation, impaired interferon (IFN) responses, and thromboinflammation, yet the mechanisms underlying endothelial dysfunction remain poorly defined. We collected 234 leftover material samples from hospitalized patients with PCR-confirmed RVIs. Patients were stratified by viral etiology, differential involvement of the respiratory tract, age and possible co-infections. Cytokines (IL-6, IL-8, IL-1β, TNF-α), IFNs (α/β/γ), and endothelial markers (ICAM-1, VCAM-1) were quantified using microfluidic immunoassays. Routine coagulation parameters were measured in a subset of patients. Compared with controls, RVI patients exhibited significantly elevated systemic cytokines (p < 0.001). IL-6 and IL-8 were higher in patients with lower respiratory tract involvement, particularly in influenza cases. Elderly patients displayed reduced IFN-α/β responses but increased proinflammatory CRP levels. Infants and children had higher ICAM-1 but lower CRP levels. Patients with viral–bacterial co-infections showed amplified IFN-γ/IL-1β/ICAM-1 response. Older adults demonstrated prolonged prothrombin times and reduced fibrinogen, indicating coagulopathy. Severe RVIs are characterized by a triad of impaired antiviral IFN responses, hyperinflammation, and endothelial activation, culminating in thromboinflammation. Age, viral type and co-infections critically shape host responses, underscoring the need for biomarker-guided, personalized therapies.

Orthobunyavirus oropoucheense (OROV) causes Oropouche fever, which exhibits symptoms similar to those of other arboviral diseases. Although it has historically been restricted to the Amazon region, the virus has recently spread to other areas of Brazil. Alagoas state, with low socioeconomic conditions and limited health coverage, has seen an increase in febrile cases without confirmed molecular diagnoses of circulating arboviruses. By September 6, 2024, 1316 samples negative for Dengue, Zika, and Chikungunya were tested for OROV and Mayaro virus using RT-qPCR, yielding 115 (8.74%) positive results for OROV. Among these, 14 (22.22%) viral isolates were obtained in Vero cells and confirmed by RT-qPCR and immunofluorescence assay (IFA). The study generated 37 new near-complete genomic sequences corresponding to the newly characterized OROV lineage and examined selection pressures on the M gene, identifying sites under purifying selection. We identified amino acid variations in the Gc glycoprotein structure at positions 507, 552, 738, and 795, which may influence host-cell interactions. This work is the first to report OROV in Alagoas, emphasizing the need for improved monitoring and control measures to mitigate public health impacts.

Drug-resistant cytomegalovirus (CMV) poses a major clinical challenge in transplant recipients, leading to treatment failure and increased morbidity. This study applied a next-generation sequencing (NGS) approach to identify antiviral resistance mutations (ARMs) in 71 samples from 68 CMV-positive patients who had undergone hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT) between 2018 and 2024. A custom nested-PCR protocol targeting six CMV genes (UL27, UL51, UL54, UL56, UL89, and UL97) was developed for enrichment prior to NGS. ARMs were detected in 23% of patients without clinical suspicion of resistance and in 62% of those with suspected resistance, most frequently affecting UL97. The most common UL97 mutations were A594V (24.4%), C603W (20.0%), and L595S (15.6%), while D301N (50%) predominated in UL54. Mutations associated with foscarnet and maribavir resistance were found in five and eight patients, respectively. NGS identified ARMs in 29 patients not detected by Sanger sequencing (p < 0.00001), while no additional ARMs were identified by Sanger alone. Importantly, these minority variants, revealed by NGS, are clinically relevant, as they may expand under antiviral pressure and contribute to virological failure. ARM presence was not significantly associated with viral load or mortality, though recurrent CMV reactivation showed a trend toward association (p = 0.0504). Survival was significantly lower in HSCT versus SOT recipients (p = 0.027). These findings support the routine clinical use of NGS for CMV resistance testing, particularly in complex cases and in the context of expanding antiviral options such as maribavir and letermovir.

There is evidence that persistent dysregulation of the immune system caused by SARS-CoV-2 infection may increase susceptibility to other infections. Here, we assessed whether it is associated with subsequent diagnoses of infectious mononucleosis due to Epstein-Barr virus (EBV-IM). Residents of Sweden aged 3–100 years without a prior diagnosis of EBV-IM were followed between January 1, 2020, and November 30, 2022, comprising a total of 9 978 860 participants. Individuals were categorized into those without a COVID-19 diagnosis, those with a positive SARS-CoV-2 polymerase chain reaction (PCR) test only – less severe exposure, and those admitted to hospital with COVID-19 – more severe exposure. Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for the association between the exposure, modeled as a time-varying covariate, and EBV-IM occurrence. EBV-IM rates per 100 000 person-years and 95% CIs were 4.6 (4.4–4.9) for individuals not diagnosed with COVID-19, 7.8 (6.9–8.9) for those with a positive SARS-CoV-2 test only, and 10.5 (6.2–17.6) for patients admitted to hospital with COVID-19. HR and 95% CI were 1.61 (1.39–1.88) for people with a positive PCR test only and 5.71 (3.33–9.79) for those admitted to hospital with COVID-19 compared with people without a COVID-19 diagnosis, after adjustment for birth year, sex, Swedish healthcare region, region of birth, and Charlson comorbidity index. SARS-CoV-2 infection was associated with a subsequent raised risk of EBV-IM, including among those with less severe acute infection, signaling immune perturbation and the possibility of further delayed sequelae linked with EBV-IM.