Journal of Medical Virology最新文献

This study aims to investigate the phenomenon of human papillomavirus (HPV) genotype switching (HGS), assess the potential influencing factors, and evaluate the clinical impact on the severity of cervical lesions. A total of 2569 HPV positive female patients with records of more than two follow-up visits were included from the gynecology department at the Obstetrics and Gynecology Hospital of Fudan University, covering the period from May 2012 to September 2022. Patients' age, treatments, vaccination, HPV genotypes before and after HGS, and the final pathology results from colposcopy were recorded. Multifactorial analyses and correlation tests were performed. Single HPV infections accounted for 67% of the total population, while multiple HPV infections comprised 33%. The most prevalent genotypes in single HPV infections were HPV52 (18.6%), HPV16 (12.28%), HPV58 (11.72%), HPV53 (8.63%), and HPV81 (6.81%). Among cases of multiple infections, the most common genotype combinations were HPV52 + HPV53 (3.02%), HPV52 + HPV58 (3.13%), and HPV52 + HPV81 (3.02%). HGS was detected in 38.2% of the total cases (458/1200). The status of medication treatment was not found to correlate with the occurrence of HGS. However, age, surgical treatment status, vaccination status, and the genotype of HPV infection may be correlated with HGS. HPV52, HPV58, HPV53, HPV56, and HPV81 showed a positive association with the occurrence of HGS transitioning from multiple infections to a single infection (HGS-MS) (p < 0.05). In contrast, HPV52, HPV16, HPV58, HPV39, HPV56, and HPV18 significantly influenced the occurrence of HGS from one single infection to another (HGS-SS) (p < 0.05), albeit negatively. Notably, only one type of HGS, HGS-MS, demonstrated a positive correlation with the severity of cervical lesions. Our findings suggest that HPV genotype switching from multiple infections to single infections is associated with cervical intraepithelial neoplasia (CIN). Different patterns of HGS could result from specific HPV genotype infections, particularly HPV16. HGS-MS is revealed to plays a catalytic role in the progression of cervical lesions.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including primary effusion lymphoma (PEL), usually seen in immunocompromised patients while lack of effective therapeutic options. Interleukin-1 (IL-1) family is a major mediator for inflammatory responses and has functional role in both innate and adaptive immunity. We previously showed high activation of multiple IL-1 signaling molecules during KSHV latent and lytic stages, as well as in clinical samples from patients with KSHV-related malignancies. In the current study, we identified RP-54745, a potential antirheumatic compound as IL-1 inhibitor, effectively repressed KSHV + PEL cell growth through inducing tumor cell apoptosis. By using an established PEL xenograft model, we found that RP-54745 treatment suppressed tumor expansion in mice. Also, RP-54745 treatment significantly reduced hyperinflammation in tumor microenvironment including myeloid cells and neutrophils infiltration, as well as blocking IL-1 signaling molecules expression in vivo. In addition, our transcriptome analysis revealed novel cellular genes and mechanisms for anticancer activities of RP-54745. Taken together, our data indicate targeting IL-1 production and signaling may represent promising therapeutic strategies against these virus-associated diseases.

The SARS-CoV-2 virus is continuously evolving, such that JN.1 and its subvariants, including KP.2, KP.3, and LB.1, are now predominant variants globally. JN.1 is derived from BA.2.86, which harbors more than 30 mutations in the spike protein compared with those of XBB and BA.2, and it carries an additional L455S mutation. Given the rapid evolution of these variants, assessing the neutralization capacity of current JN.1 lineage vaccines against prevalent variants, such as KP.3, is critical. Phylogenetic trees using spike protein sequences and antigenic cartography based on neutralization results reveal that JN.1 lineage variants are antigenically distant from previously circulating variants. Moreover, JN.1 subvariants showed inadequate neutralization titers compared with other variants against XBB.1.5-containing vaccine in mice. Immunization with vaccines targeting the JN.1, KP.2, KP.3, and LB.1 variants demonstrated significant neutralizing activity against predominant variants in mice. These results highlight the importance of vaccine development to keep pace with the evolution of SARS-CoV-2 variants and the need for updated vaccines targeting the JN.1 variant.

Infection by high-risk human papillomavirus is known to exacerbate cervical cancer development. The host immune response is crucial in disease regression. Large-scale genetic association studies for cervical cancer have identified few susceptibility variants, mainly at the human leukocyte antigen locus on chromosome 6. We hypothesized that the host immune response modifies cervical cancer risk and performed three genome-wide association analyses for HPV16, HPV18 and HPV16/18 seropositivity in 7814, 7924, and 7924 samples from the UK Biobank, followed by validation genotyping in the German Cervigen case-control series of cervical cancer and dysplasia. In GWAS analyses, we identified two loci associated with HPV16 seropositivity (6p21.32 and 15q26.2), two loci associated with HPV18 seropositivity (5q31.2 and 14q24.3), and one locus for HPV16 and/or HPV18 seropositivity (at 6p21.32). MAGMA gene-based analysis identified HLA-DQA1 and HLA-DQB1 as genome-wide significant (GWS) genes. In validation genotyping, the genome-wide significant lead variant at 6p21.32, rs9272293 associated with overall cervical disease (OR = 0.86, p = 0.004, 95% CI = 0.78-0.95, n = 3710) and HPV16 positive invasive cancer (OR = 0.73, p = 0.005, 95% CI = 0.59-0.91, n = 1431). This variant was found to be a robust eQTL for HLA-DRB1, HLA-DQB1-AS1, C4B, HLA-DRB5, HLA-DRB6, HLA-DQB1, and HLA-DPB1 in a series of cervical epithelial tissue samples. We additionally genotyped twenty-four HPV seropositivity variants below the GWS threshold out of which eleven variants were found to be associated with cervical disease in our cohort, suggesting that further seropositivity variants may determine cervical disease outcome. Our study identifies novel genomic risk loci that associate with HPV type-specific cervical cancer and dysplasia risk and provides evidence for candidate genes at one of the risk loci.

As a porcine alphacoronavirus, porcine epidemic diarrhea virus (PEDV) frequently undergoes mutations that significantly reduce the effectiveness of current prevention and control strategies, leading to recurrent outbreaks in China. This study investigates the genetic evolution and mutation patterns of the S1 protein to characterize PEDV variation in China. Genetic evolutionary analysis of 804 PEDV S1 genes, including 620 Chinese PEDV strains, revealed that 78.06% of the Chinese PEDV strains belong to the G2a-subgroup, further divided into seven branches (G2a-Clade 1-7), with the predominant strains from 2020 to 2024 being in G2a-Clade 4 (68.00%). From 2021 to 2024, 32 novel substitutions, 25 deletions, and 8 insertions were identified in the S1 protein of Chinese strains compared to those from 2010 to 2011. Notably, complete mutations were observed at amino acid sites N139D, H189Y, L229P, I287M, F345L, A361T, T499I, and A520S. Moreover, protein homology modeling analysis displayed that these deletion-insertion mutations significantly altered the surface structure of the S protein, particularly in the N-terminal domain (NTD) and receptor-binding domain (RBD) regions of S1 protein. The predictive analysis using AlphaFold3 indicated that deletion-insertion mutations in the S1-RBD region notably affected the binding affinity of the S protein to porcine DC-SIGN. These findings enhance our understanding of the genetic evolution of PEDV in China.

The determinants of varicella-zoster virus (VZV)-associated central nervous system (CNS) infection have not been fully elucidated. This study aimed to investigate the incidence and risk factors, including immunosuppression, for different manifestations of VZV-associated CNS infection. Patient registers were used to include adults diagnosed with VZV-associated CNS infections between 2010 and 2019 in Sweden. Nationwide registers covering specialized care, and regional registers covering primary care, were used. Controls without a VZV diagnosis during the study period were matched by age and sex. Risk factors were calculated using multivariable logistic regression. A total of 1488 adult cases with VZV-associated CNS infection were identified, yielding an incidence of 1.92/100 000 person-years, which increased over the study period. Meningitis was the most frequent (45%), followed by encephalitis (38%), and Ramsay Hunt syndrome (17%). The highest incidence was observed in individuals over 70 years of age (4.15/100 000 person-years), in whom encephalitis was most common. Statistically significant risk factors for VZV-associated CNS infection were HIV, hematological cancer, treatment with specific immunosuppressants or glucocorticoids, chronic obstructive pulmonary disease, diabetes, solid cancer, stroke, and congestive heart failure. Encephalitis was associated with older age, more immunosuppressive conditions, and more comorbidities than other manifestations. In conclusion, VZV is a common cause of adult viral CNS infection, for which elderly individuals with immunosuppressive or comorbid conditions are at the highest risk. The strongest risk factors found were HIV, hematological cancer, and treatment with specific immunosuppressants or high-dose glucocorticoids.

Immunity against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can be induced through either infection with the virus or vaccination, providing protection against reinfection or reducing the risk of severe clinical outcomes. In this study, we recruited 172 volunteers who received different vaccination regimens, including 124 individuals who had recovered from breakthrough infections caused by the Omicron variant (27 with 2 doses, 49 with 3 doses, and 48 with 4 doses) and 48 healthy donors who did not experience breakthrough infections (all of whom received a fourth dose during the infection wave). We measured neutralizing antibody levels against Omicron BA.5.2.48, XBB.1.5, and JN.1 and found no significant differences in neutralizing antibody titers between natural infection and homologous booster vaccination at 6 months (p > 0.05), with geometric mean titers declining by over 100-fold for some variants relative to the prototype strain.

China experienced another outbreak of acute hemorrhagic conjunctivitis (AHC) in 2023, with a total of 195 297 recorded cases. This marks the third nationwide outbreak in nearly two decades, following previous outbreaks in 2007 and 2010. Descriptive epidemiological analysis shows that the number of cases in 2023 peaked in September, similar to the last two outbreaks. The age groups with the highest incidence rate of the three outbreaks in 2007, 2010, and 2023 are 15-20, 10-15, and 10-15 years old, respectively. Students are the main occupational group in the three outbreaks. Hainan, Guangxi, and Guangdong were the top three regions with high incidence rates in the three outbreaks. In 2023, the incidence rate in Hainan Province is the highest ever. Pathogenetic analyses show that the pathogens isolated during the 2023 outbreak were identified as the GIV genotype of CVA24v. Seven different recombination patterns were identified in the recombination analysis of the Chinese strains in 2023 and representative strains of global outbreaks since 1988. These patterns mainly involved the recombination signals of EV-C96 and PV in the 5' untranslated region and 3C and 3D regions. Although recombination events of CVA24v are rarely reported, its recombination was consistently present through systematic analysis in this study. This study comprehensively analyzed the 2023 AHC re-emerging data and isolated CVA24v sequences, providing valuable data for future CVA24v molecular epidemiology studies.

The study aims to investigate the key risk factors influencing the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS) and develop a prognostic warning model based on these factors. A total of 264 SFTS patients treated at Tongji Hospital from April 1, 2023, to July 30, 2024, were included as the research sample. Retrospective analysis was conducted based on the final prognostic status of the patients, dividing them into a survival group (n = 165) and a death group (n = 99). Univariate and multivariate analyses were performed along with LASSO and logistic regression on baseline information and the first laboratory indicators within 24 h after admission to identify independent risk factors affecting prognosis. A warning model was constructed based on these factors. The analysis revealed that age (OR = 1.098, 95% CI: 1.054-1.149, p < 0.001), presence of consciousness disorders (OR = 2.506, 95% CI: 1.042-6.187, p = 0.042), BUN (OR = 1.248, 95% CI: 1.154-1.369, p < 0.001), and viral load (OR = 3.598, 95% CI: 2.572-5.288, p < 0.001) were identified as independent risk factors significantly impacting the prognosis of SFTS patients. A nomogram warning model was developed incorporating these four risk factors, which demonstrated excellent predictive performance (ROC = 0.917, 95% CI: 0.882-0.948, p < 0.001). The prognostic risk prediction model successfully established for SFTS patients in this study exhibits robust predictive performance, and it is anticipated to serve as a practical clinical tool for predicting disease progression and prognosis in SFTS patients.

Despite viral suppression with antiretroviral therapy, immune nonresponders (INR) among people living with HIV (PLWH) still have a higher risk of developing AIDS-related and non-AIDS-related complications. Our study aimed to investigate the phenotype and functions of Natural Killer (NK) cells in INR, to better understand underlying mechanisms of immune nonresponse. Our cross-sectional study included PLWH aged over 45 with an undetectable HIV viral load sustained for at least 2 years. Participant CD4⁺ T-cell counts exceeded 500 cells/mm³ for IR or below 350 cells/mm³ for INR. We characterized NK cell subsets, performed natural cytotoxicity and ADCC assays, and phenotyped NK cells before and after functional assays. Median CD4 levels were 247.5 (IQR, 208.8-286.3) cells/mm³ and 768.5 (IQR, 673.3-957.8) cells/mm³ in the INR (n = 20) and IR (n = 40), respectively. NK cell counts were lower in INR (p = 0.00066), but the percentages were similar between IR and INR. NKG2A was the only differentially expressed marker between groups, showing higher expression in INR. Additionally, NK cell natural cytotoxicity was elevated in the INR group. Multivariate analyses associated CD4 nadir and low NK cell count with immune nonresponse. Our results do not indicate a clear role for NK-mediated ADCC in immune nonresponse. We did not objectify an association between CD8 hyperactivation and INR.