Journal of Medical Virology最新文献

Hematological neoplasms (HN) are disorders originating in blood cells that hold significant epidemiological importance. Treatments available for these conditions can induce immunosuppression, and it increases the risk of viral infections and reactivations, mainly by Human betaherpesviruses (HCMV, HHV-6, and HHV-7). Studies have suggested that these viruses play potential oncogenic role in hematological neoplasms, although results remain inconclusive. This study aimed to evaluate the frequency and viral load of betaherpesviruses in saliva samples from patients with hematological neoplasms, and to explore their relevance to clinicopathological characteristics. In total, 260 saliva samples collected from patients with Hodgkin lymphoma (HL) (n = 29), non-Hodgkin lymphoma (NHL) (n = 106), leukemia (n = 85) and multiple myeloma (MM) (n = 40) were analyzed in multiplex qPCR. The result was compared with control group samples from patients without hematological neoplasm (n = 159). HHV-7 was the most frequently detected betaherpesvirus, identified in 15.8% (41/260) of patients with hematological neoplasms. In comparison, HCMV and HHV-6 were detected in 12 (4.6%) and 11 (4.2%) patients, respectively. In the control group, HCMV was detected in 2 individuals (1.3%), HHV-6 in 6 (3.8%), and HHV-7 in 14 (8.8%). A statistically significant difference in HHV-7 detection was observed between patients and controls (p = 0.005). Additionally, HCMV detection showed a significant difference between patients with HL and MM (p = 0.036). The detection of betaherpesviruses, particularly HHV-7, was more frequent and viral in patients with hematologic malignancies compared to the control group, with statistically significant differences observed. In summary, HHV-7 was the most frequently detected virus, found in 15.8% of patients versus 8.8% of controls. However, its presence in saliva alone does not confirm disease association. Our findings reinforce the need for longitudinal studies to clarify the potential pathogenic role of HHV-7 and other betaherpesviruses in hematological neoplasms, and their possible impact on patient outcomes.

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.