Journal of Medical Virology最新文献

Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is an intractable form of epilepsy involving the hippocampus, and temporal lobectomy remains an effective treatment. Human herpesvirus 6B (HHV-6B) establishes latency in the hippocampus and may contribute to MTLE-HS pathogenesis by altering host gene expression; however, transcriptomic data from healthy controls remain limited. This study investigated the role of HHV-6B to MTLE-HS pathogenesis by analyzing gene expression in resected hippocampal tissues. Samples were collected from 12 to 43 HHV-6 DNA-positive and -negative patients, respectively, and three controls. RNA sequencing was performed on eight representative samples, followed by RT-qPCR validation of nine selected genes in 58 samples. RNA sequencing identified 600 differentially expressed genes (210 upregulated, 390 downregulated) between HHV-6B-positive MTLE-HS and controls. Pathway enrichment analysis revealed involvement of synaptic signaling and inflammatory responses, with prostaglandin biosynthesis specifically upregulated in HHV-6B-positive tissues. Two genes were significantly upregulated in HHV-6B-positive compared with HHV-6B-negative samples. RT-qPCR confirmed elevated cholesterol 25-hydroxylase and interleukin 1 beta expression in HHV-6 DNA-positive samples (both p = 0.031). These findings suggest that HHV-6B may contribute to MTLE-HS pathogenesis by modulating the expression of host inflammatory genes, supporting a role for neuroinflammation and the potential benefits of anti-inflammatory therapies.

With the rapid development and maturation of high-risk human papillomavirus (hrHPV) genotyping kits, it is crucial to understand the specific patterns of methylation in different hrHPV statuses, rather than simply categorizing them as hrHPV positive or negative. To achieve this goal, we first assessed the prevalence and CIN3+ risk of specific hrHPV genotypes in 184 cervical scrapings and then evaluated the performance of five host genes methylation to distinguish CIN3+ from <CIN3 not only among hrHPV-positive and hrHPV-negative women, but also among women positive for HPV16, HPV18, HPV52, and HPV58. The results showed that women with HPV16 infections had a higher risk of developing CIN3+ than women with other hrHPV infections. More importantly, we found that hrHPV testing caused a high false-positive rate (43.54%) and leading to over-referral of <CIN3 cases. Triage of patients with HPV 52/58 positive using ZIC1^m could accurately identify all CIN3+ cases to avoid over-referral of false-positive cases. In addition, implementing primary hrHPV testing resulted in 5.7% of CIN3+ patients being missed in our study. Our exploratory analysis found that DNA methylation of specific genes, including ZIC1^m, ZNF582^m, PAX1^m, and MIR129-2^m, could lower the high false-positive rate and find 80% (4/5) missed CIN3+ cases caused by hrHPV testing. This study substantiates the dual role of DNA methylation detection in cervical cancer screening. By incorporating methylation detection, the existing HPV-based screening strategy can be further optimized to achieve precise risk stratification and facilitate the shift from cervical cancer screening to personalized and precise management.

Varicella zoster virus (VZV) infection is typically mild in children but may result in severe complications in some cases. Environmental lead exposure is known to impair immune function; however, its relationship with VZV-specific humoral immunity has not been well characterized. We analyzed data from 7,938 participants aged 6–19 years from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 to examine the association between blood lead levels (BLL) and VZV IgG concentrations. Multivariable linear regression models were used to evaluate this association, and dose–response relationships were explored to assess potential nonlinearity. After adjustment for potential confounders, higher BLL was significantly associated with lower VZV IgG levels (β = −0.24, 95% CI: −0.43, −0.05, p = 0.013), with no evidence of effect modification by demographic or metabolic factors. A nonlinear dose-response relationship was identified, with a stronger inverse association observed below the inflection point of 1 μg/dL (β = −1.23, 95% CI: −2.22, −0.24) compared with levels above this threshold (β = −0.14, 95% CI: −0.35, 0.08); the log-likelihood ratio test confirmed significant nonlinearity (p = 0.045). These findings suggest that even low-level lead exposure may be associated with reduced VZV IgG concentrations among U.S. children and adolescents, highlighting potential immunological effects of environmental lead exposure.

The factors involved in the development of functional dependence, pain and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) could be linked to inflammatory cytokines and proviral load. This study aimed to assess the association between myelopathy, pain, and functionality with proviral load in blood, serum levels of cytokines and the interleukin 6 (IL-6) polymorphism in individuals living with HTLV-1. This was a cross-sectional study. Consecutive HTLV-1-infected patients, with or without HAM/TSP, attending the infectious diseases clinic were included. A semi-structured questionnaire, functional independence measure, and the numerical rating scale for pain intensity were applied and peripheral blood samples were collected. Plasma cytokines were determined by flow cytometry. Genotyping for the IL-6 gene polymorphism rs2069849 (A > G) was performed using a TaqMan allelic discrimination assay. The proviral load was determined by Real-time polymerase chain reaction. 165 patients were included, 72% women (aged 52 ± 13.1 years), 23% were functionally dependent, and 21% had HAM/TSP. Patients functionally dependent had higher IL-6 and IL-8 levels and lower IL-10 levels. HAM/TSP patients also showed higher IL-6 and IL-8. No associations were observed between any cytokine and chronic pain, pain frequency or intensity. Neither IL-6 polymorphism nor proviral load showed any association with myelopathy, pain, or functionality.