Journal of Medical Virology最新文献

As the COVID-19 pandemic continues, increasingly complex vaccination and infection histories have made it urgent to investigate the antibody dynamics in populations with hybrid immunity. This study aimed to explore the multi-time-point dynamics of SARS-CoV-2 IgG antibody levels in a community-based population in Jiangsu Province, China, following the Omicron BA.5 wave, as well as the long-term persistence of IgG antibodies nearly 2 years postinfection. A total of 2737 participants across Jiangsu Province were followed up at three different time points over a 6-month period (December 2022-June 2023). Additionally, a cross-sectional serological survey was conducted in October 2024, involving 230 participants to assess long-term antibody persistence. We used generalized additive models to fit antibody dynamics curves, generalized linear mixed models to explore factors influencing antibody levels, and Kaplan-Meier survival analysis to estimate cumulative seroreversion rates. Our findings revealed that, following the large-scale Omicron BA.5 infections, over 85% of the population initially exhibited seropositive IgG levels. Older individuals (> 65 years) had significantly lower antibody levels and faster rates of decline compared to younger participants. Booster immunization reduced the risk of seroreversion by 59.79% (95% CI: 29.63%-76.46%), while individuals with multiple infections experienced slower antibody decay. In the cross-sectional survey conducted 22 months postinfection, the IgG seropositivity rate remained high, exceeding 98%, indicating sustained immunity at the population level. This study provides valuable insights into the dynamics and persistence of IgG antibody levels following large-scale infection. The results underscore the importance of tailored booster immunization strategies to sustain long-term immunity, especially in vulnerable groups like the elderly. Additionally, ongoing serological monitoring is essential for assessing population immunity and informing future vaccination strategies.

Glucose-regulated protein 78 kDa (GRP78), a key marker of endoplasmic reticulum stress (ERS), is upregulated in hepatocellular carcinoma (HCC) tissues, but its role in hepatitis B virus (HBV)-induced tumorigenesis remains unclear. This study aimed to investigate the contribution of GRP78 to HBV-associated tumor development and explore the ERS pathways involved. The results showed that increased GRP78 expression in patients with HBV-related HCC was associated with a poor prognosis within the first 2 years following diagnosis. Furthermore, using wild-type HBV strain and the oncogenic HBV rtA181T/sW172* mutant, this study demonstrated that the HBV-induced GRP78 expression correlated with elevated reactive oxygen species (ROS) levels. Moreover, GRP78 expression enhanced hepatocyte proliferation and resistance to apoptosis. In wild-type HBV-infected hepatocytes, GRP78 suppressed apoptosis by inhibiting the PERK/p38 pathway. In contrast, the HBV rtA181T/sW172* mutation led to increased GRP78 expression and inhibition of cell apoptosis through activation of the IRE-1α/XBP1/BCL-2 pathway. In conclusion, GRP78 plays a pivotal role in HBV-induced hepatocarcinogenesis by modulating distinct ERS pathways. Targeting these pathways may aid in the therapeutic management of HBV-associated hepatocarcinogenesis.

Studies investigating the impact of donor cytomegalovirus (CMV) positivity on the prognosis of liver transplantation (LT) recipients with HCC are currently lacking. A total of 21 759 eligible LT recipients were identified in the UNOS database between January 2002 and June 2023. The patients were divided into the donor CMV-seronegative (n = 7575) and CMV-seropositive (n = 14 814) groups. Moreover, the subgroup analyses by recipient age and gender were conducted. All patients were also divided into 18-40 (n = 271), 40-60 (n = 9538), and ≥ 60 (n = 11 950) groups, male (n = 16 954) and female (n = 4805) groups, respectively. Patients in the donor CMV-seropositive group had shorter overall survival (OS) and disease-free survival (DFS) compared to those in the donor CMV-seronegative group (both p < 0.001). Donor CMV seropositivity was proved to be a risk factor for OS and DFS (both p = 0.001). Patients receiving CMV-seropositive liver grafts had shorter OS and DFS in the 40-60 and ≥ 60 groups (all p < 0.05). Patients receiving CMV-seropositive liver grafts had shorted OS and DFS only in the male group (both p < 0.001). The receipt of donor CMV-seropositive liver grafts is associated with shorter survival and a higher risk of HCC recurrence in LT recipients with HCC. These adverse effects are influenced by recipient age and gender.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and notable public health impact, caused by a novel phlebovirus, primarily transmitted through infected tick bites. This study aimed to assess the prevalence of co-infections among hospitalized patients with SFTS, characterize isolated pathogens, and evaluate demographics, clinical features, and laboratory variations to identify potential risk factors for co-infections. In a cohort of 78 SFTS patients categorized into co-infection and non-co-infection groups, 44.9% (35/78) experienced co-infections, with a 25.7% mortality rate in that subgroup. Pulmonary and bloodstream infections, particularly fungal infections, were most common, and earlier onset of co-infections correlated with higher fatality. Univariable logistic regression identified significant risk factors, followed by multivariable analysis to determine independent predictors. Changes in mental status, hemorrhage, deep venous or arterial catheterization, mechanical ventilation, activated partial thromboplastin time (APTT) > 55 s, albumin < 37.5 g/L, interleukin-6 > 18.700 pg/mL, and interleukin-10 > 21.300 pg/mL emerged as significant risk factors, with hemorrhagic symptoms and low albumin remaining independent predictors. Internal validation through bootstrap resampling yielded a mean area under the receiver operating characteristic curve of 0.795 (95% CI: 0.706-0.868). These findings suggest that early recognition of these predictors may improve co-infection management in SFTS patients, leading to better clinical outcomes and more informed clinical decisions.

We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis. Notably, gaps in the spike-encoding gene led us to design new primers and perform Sanger sequencing, which revealed high similarities to MERS-related (MERSr) CoV strains found in humans and camels. Additionally, we identified key residues in the receptor-binding domain (RBD) of the spike protein, suggesting potential interactions with DPP4, the receptor for MERSr-CoV. Our analyses also revealed evidence of recombination involving our laboratory-produced sequences. These findings highlight the extensive genetic diversity of CoVs, the presence of novel viral lineages, and the occurrence of recombination events among bat CoVs circulating in Brazil, underscoring the critical role bats play as reservoirs for emerging viruses and emphasizing the necessity of ongoing surveillance to monitor the public health risks associated with CoV spillover events.

The impact of human cytomegalovirus (HCMV) infection on the mid- and long-term balance between pro-inflammatory and anti-inflammatory cytokines among kidney transplant recipients (KTRs) remains unclear. We measured plasma levels of 12 Th1/Th2-type cytokines (granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-18 and tumor necrosis factor-α) in a cohort of 290 KTRs at four time points through month 12 after transplantation. Cytokine levels at each point were compared according to the previous documentation of HCMV replication by two approaches: "cumulative exposure" from the time of transplantation and "recent exposure" within the 2-3 months preceding cytokine assessment. Significance levels were Bonferroni-corrected for multiple pairwise comparisons. Plasma levels of IL-6, IL-10, and IL-12p70 at month 1 were significantly increased in KTRs that had experienced HCMV infection during the first 30 days. By month 3, IL-6 and IL-10 remained increased in KTRs with cumulative exposure through day 90. Cumulative exposure to HCMV replication through day 180 was also associated to increased IL-10 levels at month 6. In addition, KTRs with recent HCMV exposure had increased IL-10 levels at months 3 and 6. After multivariable adjustment, cumulative exposure to HCMV infection and/or the area under curve of HCMV DNAemia during the corresponding period were associated to IL-10 levels within the highest quartile at months 1, 3, and 6. Preceding HCMV infection induces sustained changes in the plasma cytokine milieu of KTRs, with elevated IL-6 and IL-10 levels throughout the first 6 months after transplantation.

To evaluate the performance of three rapid influenza diagnostic tests (RIDTs) for detecting influenza A and B viruses compared to RT-PCR. A total of 291 subjects with acute respiratory infections were enrolled. Respiratory specimens were collected and tested for influenza A and B viruses using three RIDTs. The results were compared with those obtained using an RT-PCR assay from Shanghai Berger Medical Technology Co. Ltd. as the reference method. Among the 291 subjects, 119 (40.9%) tested positive for influenza A virus and 38 (13.1%) for influenza B virus by RT-PCR. The sensitivities of the three RIDTs for influenza A virus were 92.4%, 89.1%, and 79.8%, respectively, while their specificities were 98.8%, 98.8%, and 100%, respectively. For influenza B virus, the sensitivities of the three RIDTs were 92.1%, 92.1%, and 73.7%, respectively, and their specificities were 100%, 100%, and 100%, respectively. The positive predictive values (PPVs) for influenza A virus were 98.2%, 98.1%, and 100%, respectively, while the negative predictive values (NPVs) were 94.5%, 92.4%, and 86.9%, respectively. For influenza B virus, the PPVs were all 100%, and the NPVs were 99.2%, 99.2%, and 97.7%, respectively. The three evaluated RIDTs demonstrated high specificity but varied sensitivity for detecting influenza A and B viruses. Negative results from RIDTs should be confirmed by RT-PCR, especially during peak influenza seasons. The high PPVs suggest that positive RIDT results are reliable for influenza diagnosis, while the high NPVs indicate that negative results are more likely to be true negatives.

Epstein-Barr virus (EBV) is a ubiquitous human ɣ-herpesvirus implicated in various malignancies, including Burkitt's lymphoma and gastric carcinomas. In most EBV-associated cancers, the viral genome is maintained as an extrachromosomal episome by the EBV nuclear antigen-1 (EBNA1). EBNA1 is considered to be a highly stable protein that interacts with the ubiquitin-specific protease 7 (USP7). Here, we show that pharmacological inhibitors and small interfering RNA (siRNA) targeting USP7 reduce EBNA1 protein levels in a proteosome-dependent manner. Proteomic analysis revealed that USP7 inhibitor GNE6776 altered the EBNA1 protein interactome, including disrupting USP7 association with EBNA1. GNE6776 also inhibited EBNA1 binding to EBV oriP DNA and reduced viral episome copy number. Transcriptomic studies revealed that USP7 inhibition affected chromosome segregation and mitotic cell division pathways in EBV⁺ cells. Finally, we show that GNE6776 selectively inhibited EBV⁺ gastric and lymphoid cell proliferation in cell culture and slowed EBV⁺ tumor growth in mouse xenograft models. These findings suggest that USP7 inhibitors perturb EBNA1 stability and function and may be exploited to treat EBV latent infection and tumorigenesis.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease with a high fatality rate. The clinical diagnosis criteria mainly rely on white blood cell (WBC) and platelet (PLT), which, however, are of limited usage in identifying atypical SFTS. A multicenter study was performed in two hospitals from 2011 to 2023. SFTS patients were categorized as atypical or typical based on the clinical diagnosis criteria. Clinical progress and outcomes were compared between the two groups. A total of 2876 laboratory-confirmed SFTS patients were included in this study, 90.54% (2604/2876) of whom exhibited both thrombocytopenia and leukopenia and were defined as typical SFTS patients, while 9.46% (272/2876) were defined as atypical SFTS patients. Patients with typical SFTS were more likely to develop complications (adjusted odds ratio [OR] = 2.09, 95% confidence interval [CI]:1.48-2.92, p < 0.001) and fatal outcomes (adjusted OR = 2.24, 95% CI: 1.37-3.89, p = 0.002) compared to patients with atypical SFTS. Among atypical patients, those with decreased PLT and normal WBC levels (PLT↓ and WBC→) experienced increased complication rates (adjusted OR = 2.76, 95% CI: 1.30-6.05, p < 0.001) compared to those with decreased WBC and normal PLT (WBC↓ and PLT→). In the typical group, 238 patients developed thrombocytopenia earlier than leukocytopenia (defined as the TL group), while 311 subjects developed leukocytopenia earlier than thrombocytopenia (defined as the LT group). Compared to the LT group, patients in the TL group were more likely to develop fatal outcomes (HR = 1.91, 95% CI: 1.04-3.50). These findings highlight the presence of atypical SFTS cases that did not meet the clinical diagnosis criteria. Clinical profiles and outcomes differed between typical and atypical SFTS patients. A less stringent diagnostic criterion than combined thrombocytopenia and leukopenia is suggested for making clinical diagnoses within 7 days of disease onset.

Small-cell neuroendocrine cancer (SCNEC) of the uterine cervix is an exceedingly rare, highly aggressive tumor with an extremely poor prognosis. The cellular heterogeneity, origin, and tumorigenesis trajectories of SCNEC of the cervix remain largely unclear. We performed single-cell RNA sequencing and whole-exome sequencing on tumor tissues and adjacent normal cervical tissues from two patients diagnosed with SCNEC of the cervix. Here, we provide the first comprehensive insights into the cellular composition, HPV infection-related features, and gene expression profiles of SCNEC of the cervix at single-cell resolution. Correlation analyses suggested that SCNEC of the cervix may originate from squamous epithelial cells, and this observation was validated with bulk RNA-seq data from external cervical neuroendocrine cancer. Furthermore, sex-determining region Y-box 2 (SOX2), a key transcription factor that functions in direct neural differentiation, was located in the copy number gain region and highly expressed in neuroendocrine tumor cells from both patients. Notable, the distributions of the HPV-infected epithelium and SOX2 highly expressed epithelium were consistent with each other. Therefore, we supposed that high-risk HPV infection and amplification of SOX2 in the squamous epithelium may contribute to the progression of small-cell neuroendocrine tumorigenesis in the cervix.