Journal of Medical Virology最新文献

Coxsackievirus A2 (CVA2), a member of enterovirus A species (EV-A), is associated with diverse human diseases and occasionally causes acute gastroenteritis (AGE). In Thailand, CVA2 emerged as the predominant genotype in 2019. The increasing incidence of CVA2, coupled with the limited availability of full-length genomes, highlights the need for more complete genome sequence analysis to facilitate molecular epidemiology study. This study aimed to investigate the molecular epidemiology, evolutionary dynamics, and recombination characteristics of CVA2 associated with AGE in Thailand from 2013 to 2022. A total of 19 full-genome sequences of CVA2 isolated from stool samples of AGE patients in Thailand were characterized and analyzed together with the reference sequences available in the GenBank database. A novel lineage of CVA2 (subgenotype C5) was detected with the potential recombination with CVA10 within the P2 and P3 regions. Specific consensus amino acid mutations, A61S in the VP3 gene and R136K in the 3D (RdRp) gene, were identified in all CVA2 recombinant strains. Additionally, the S45G mutation in the RdRp gene was found to be potentially associated with the emergence of CVA2 infection in 2019. In conclusion, this study reveals potential intertypic recombinant events and specific mutations in CVA2 strains isolated from AGE patients and provides a broader understanding of its evolutionary epidemiology.

Studies have suggested an association between polymorphisms in class I genes of the major histocompatibility complex, specifically the human leukocyte antigen (HLA), and susceptibility to SARS-CoV-2. To explore this, 135 individuals with positive serological tests for SARS-CoV-2 were recruited. All the samples were collected before the advent of vaccines, avoiding immunization effects. Participants were divided into high and low neutralizing antibody titer groups, and polymorphisms in HLA-A, HLA-B, and HLA-DRB1 genes were examined using PCR-SSO. Allele prevalence in the study population was compared to the National Bone Marrow Volunteer Donors Register (REDOME) in São Paulo and between the high and low titer groups within the study population. Results indicated that the HLA-B*15 polymorphism was more prevalent in the COVID-19 positive group compared to the control population (COVID-19 = 0.1370; Control = 0.0875; p = 0.0067). The HLA-B*18 polymorphism was less prevalent in the COVID-19 group (COVID-19 = 0.0185; Control = 0.0534; p = 0.0064). Additionally, the HLA-A*30 polymorphism was more prevalent in the high titer group within the (high = 0.10937; low = 0.02816; p = 0.0125). Other polymorphisms showed no significant differences. These findings align with international studies, suggesting these genes plays a role in COVID-19 pathophysiology, however, further research is required to fully understand their impact.

Adult T-cell leukemia (ATL) is an aggressive malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) infection. Enhancer of zeste homolog 2 (EZH2) has been implicated in the development and progression of multiple cancers, including virus-induced malignancies. However, the potential function of EZH2 in HTLV-1-induced oncogenesis has not been clearly elucidated. In the present study, we showed that EZH2 was overexpressed and activated in HTLV-1-infected cell lines, potentially due to the activation of EZH2 promoter by HTLV-1 Tax and NF-κB p65 subunit. In addition, we found that EZH2 enhanced the HBZ-induced activation of TGF-β signaling in a histone methyltransferase-independent manner. As a mechanism for these actions, we found that EZH2 targeted Smad3/Smad4 to form a ternary complex, and the association between Smad3 and Smad4 was markedly enhanced in the presence of EZH2. Knockdown of EZH2 in ATL cells indeed repressed the expressions of the TGF-β target genes. In particular, EZH2 synergistically enhanced the HBZ/TGF-β-induced Foxp3 expression. Treatment of 3-Deazaneplanocin A, a specific inhibitor of EZH2 significantly inhibited the Foxp3 expression. Taken together, our results suggest that EZH2 may be involved in the differentiation of regulatory T cells through activating the HBZ-Smad3-TGF-β signaling axis, which is considered to be a key strategy for viral persistence.

Fragility fractures are a significant concern among people living with HIV(PLWH) due to the combined effects of chronic inflammation, immune dysregulation, and antiretroviral therapy. Traditional biomarkers have limited predictive value for fragility fractures in this population. This study aims to evaluate the systemic immune inflammation-based scores as novel biomarkers for predicting fragility fractures in PLWH in China. We conducted a cohort study of PLWH in the orthopedic department of Beijing Ditan Hospital from January 2011 to September 2023. We monitored fragility fractures and collected data on demographics, clinical characteristics, and laboratory parameters. Multivariate Cox and logistic regression models were used to assess the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) for fragility fractures. Restricted cubic splines (RCS) were employed to explore potential nonlinear relationships, and subgroup analyses were conducted to examine the stability of these associations. During a median follow-up of 5.5 years, our study included 1148 PLWH patients, and 204 patients (17.8%) experienced fragility fractures. After adjusting for all covariates, SII and SIRI were identified as independent risk factors for fragility fractures in PLWH, whereas NLR, PLR, and MLR were not. Patients with higher levels of SII and SIRI had a significantly increased risk of fragility fractures compared to those with lower levels (HR: 1.96, 95% CI: 1.24–3.10, p = 0.004; HR: 1.83, 95% CI: 1.16–2.88, p = 0.009). RCS analysis indicated a stable linear relationship between SIRI and fragility fractures. Furthermore, KM curves demonstrated that patients with higher SII and SIRI scores had a higher likelihood of experiencing fragility fractures. Our research shows that SII and SIRI are promising biomarkers for predicting fragility fractures in PLWH. Clinicians should consider incorporating SIRI into clinical practice to improve fracture risk stratification and guide preventive strategies for this vulnerable population.

Enterovirus A71 (EVA71) is a leading causative agent of hand, foot, and mouth disease, posing a significant threat to the health of young children, particularly in the Asia-Pacific region. Currently, there is no specific antiviral drug for EVA71 infection; therefore, early and rapid diagnosis is critical for disease prevention and control. Here, we report the development of a simple, rapid, and sensitive detection method for EVA71 infection using reverse transcription-multiple cross displacement amplification (RT-MCDA) combined with nanoparticle-based lateral flow biosensors (LFB). In the RT-MCDA system, a set of 10 primers was designed to target the highly conserved region of the VP1 gene of EVA71 and amplify the genes in an isothermal amplification device. The RT-MCDA amplification reaction products could then be identified by visual detection reagent (VDR) and LFB without the need for specialized equipment. The results demonstrated that the optimal reaction condition for the EVA71-RT-MCDA assay was 65℃ for 40 min. The EVA71-RT-MCDA assay could detect as low as 40 copies of plasmid and 50 copies of pseudotyped virus in a reaction. No cross-reaction was found between EVA71 strains and non-EVA71 strains. For 125 clinical anal swab samples, with EVA71-RT-MCDA assay, 30 samples were positive, which was in consistent with the the conventional real-time quantitative reverse transcription polymerase chain reaction assays. The entire procedure, including a 15-min specimen processing step, a 40-min MCDA reaction, and result reporting within 2 min, was completed in less than 60 min. In conclusion, the EVA71-RT-MCDA-LFB assay targeting the VP1 gene is a rapid, highly sensitive, simple, and specific test that could be widely applied in point-of-care settings and basic medical facilities in rural areas.

Herpes simplex virus (HSV) infections, primarily caused by HSV-1 and HSV-2, are prevalent worldwide and carry significant health implications. The impact of tobacco use on HSV infections, however, remains underexplored. This cross-sectional study utilized the National Health and Nutrition Examination Survey (NHANES) database (2009–2016) to investigate the link between Tobacco use and HSV infections among U.S. adults. Smoking status, volume, and serum cotinine levels were analyzed, alongside demographic and behavioral factors. Propensity score matching (PSM) was employed to adjust for confounders such as sexual behavior. Our study involved 5693 participants to explore the relationship between tobacco use and HSV infection. We found that smokers, particularly current smokers, have a significantly increased risk of both HSV-1 and HSV-2 infections compared to non-smokers. Specifically, the adjusted odds ratio (OR) for HSV-1 in current smokers was 1.36 (95% CI: 1.16–1.59, p < 0.001), and for HSV-2, it was 2.37 (95% CI: 1.88–3, p < 0.001). The risk escalates with the intensity of smoking. Elevated serum cotinine levels correlated with an increased risk of HSV infection (HSV-1:1.13 [95% CI:1.09–1.18, p < 0.001]; HSV-2:1.33 [95% CI:1.25–1.41, p < 0.001]). After PSM for factors such as age, gender, sexual behavior, and condom use, these associations remained significant. Tobacco use is significantly associated with an increased risk of HSV infections, highlighting the importance of reducing tobacco exposure in public health strategies against HSV. Further, longitudinal studies are warranted to establish causality and explore underlying mechanisms.

Describing the transmission characteristics among older adults is essential for designing tailored interventions. An epidemiological investigation combined with phylogenetic analysis was conducted to reveal potential transmission linkages among older adults in Nanjing. Between 2018 and 2022, 188 pol sequences were successfully amplified. Multiple genotypes were identified, including CRF07_BC (55.3%), CRF01_AE (30.3%), CRF08_BC (8.0%), B (3.2%), CRF55_01B (1.1%), CRF67_01B (0.5%), CRF68_01B (0.5%), and unique recombinant forms (URF) (1.1%). Transmission network analysis identified 120 genetically linked patients forming 23 clusters, ranging from 2 to 26 individuals. Multivariable logistic regression analysis showed that compared with farmers and heterosexuals, patients with other occupations (OR = 0.404, 95% CI: 0.173−0.945) and MSM (OR = 0.193, 95% CI: 0.050−0.738) were less likely to have high linkage. Subjects who lived in suburban areas were more likely to have high linkage (OR = 10.932, 95% CI: 3.335−35.830). The Sankey diagram suggested that patients living in suburban areas primarily transmitted the disease within the local district (χ² = 24.192, p < 0.001). Among the 188 pol sequences, the prevalence of pretreatment drug resistance was 8%. In suburban areas with a rising HIV-1 epidemic, improving early detection and timely treatment is critical. More tailored interventions for this subgroup are urgently needed.