Journal of Medical Virology最新文献

Previous reports have indicated that during the era of combination antiretroviral therapy, the major causes of morbidity and mortality in people living with HIV (PLWH) were not solely linked to HIV-related opportunistic infections but also to cancers that were difficult to manage due to HIV-related immunodeficiency. We investigated whether PLWH who underwent autologous hematopoietic stem cell transplantation (ASCT) for lymphomas experienced significant morbidity over the past thirty years following HIV infection. We conducted a retrospective follow-up study of 49 PLWH over a 10-year period following ASCT. We collected survival data, examined the occurrence of long-term events, assessed CD4 + T-cell immune recovery, and analysed the correlation between immune recovery and the events experienced by these patients. The data confirmed the significant long-term effectiveness of ASCT, with an overall survival rate of 78% at 10 years post-ASCT. Opportunistic infections, which occurred soon after ASCT and were associated with lower CD4 + T-cell counts, were successfully managed. However, lymphoma relapse, secondary malignancies, cardiovascular disease, and bone disease, which developed years after ASCT, were major causes of morbidity and mortality in this population. Our findings highlight the need for the development and validation of specific tests to predict risk and guide effective interventions for metabolic diseases, secondary malignancies, and lymphoma relapses in PLWH treated with ASCT for lymphoma.

We detected an emerging human-associated gemykibivirus-2 (HuGkV-2) in rectal swab sample from Molossus molossus bat from Brazil. Phylogenetic analysis further revealed well-supported relationships between our sequence and those associated with human infections. This study underscores the necessity of ongoing monitoring of HuGkV-2 to elucidate potential spillback events, its role in human infections, and its public health implications.

We investigated whether antibody concentrations measured in plasma using the Roche Elecsys® Anti-SARS-CoV-2 S assay (targeting the receptor binding domain, RBD) could estimate levels of Wuhan-Hu-1 and Omicron XBB.1.5 spike-directed antibodies with neutralizing ability (NtAb) or those mediating NK-cell activity. We analyzed 135 plasma samples from 39 vaccinated elderly nursing home residents. A strong correlation was found for NtAb against both Wuhan-Hu-1 (Rho = 0.73, p < 0.001) and Omicron XBB.1.5 (sub)variants (Rho = 0.73, p < 0.001). Moderate positive correlations were observed for NK-cell activity, based on lysosome-associated membrane protein 1 (LAMP1)-producing NK cells stimulated with Wuhan-Hu-1 (Rho = 0.43, p < 0.001) and Omicron XBB.1.5 spike proteins (Rho = 0.50, p < 0.001). Similarly, interferon-gamma (IFN-γ)-producing NK-cell frequencies showed moderate correlations (Wuhan-Hu-1: Rho = 0.43, p < 0.001; Omicron XBB.1.5: Rho = 0.50, p < 0.001). Random Forest models accurately predicted NtAb levels against Wuhan-Hu-1 (R² = 0.72), though models for Omicron XBB.1.5 were less robust. Anti-RBD antibody concentrations of 4.73 and 5.02 log₁₀ BAU/mL predicted high NtAb levels for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. Antibody thresholds for predicting functional NK cell-mediated responses were 4.73 log₁₀ and 4.54 log₁₀ BAU/mL for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. For LAMP1-producing NK cells, the thresholds were 4.94 and 4.75 log₁₀ BAU/mL for Wuhan-Hu-1 and Omicron XBB.1.5, respectively. In summary, total anti-RBD antibody levels measured by the Roche assay may allow inference of NtAb levels and, to a lesser extent, Fc-mediated NK-cell responses against Omicron XBB.1.5.

Three hospitals implemented molecular point-of-care tests (POCTs) to screen patients for SARS-CoV-2 infection upon admission during the 2021/2022 influenza season, which in Belgium lasted from January to April 2022. The samples were simultaneously tested for influenza A/B. Influenza positivity at admission was examined in relation to patient characteristics and symptomatology. Influenza POCTs were performed on all patients requiring urgent hospitalization, regardless of the admission reason. A total of 9327 patients were included in the study, of which 411 (4.4%) tested positive for influenza A/B. Asymptomatic infection and mild illness accounted for respectively 11.2% (95% CI: 8.5%-14.6%), and 43.3% (95% CI: 38.6%-48.1%) of the cases. A total of 66% (95% CI: 60%-72%) of all patients in these symptom categories (asymptomatic and mild illness) showed a high viral load (cycle threshold [Ct] < 24). Only in 30 (7.3%, 95% CI: 5.2%-10.2%) of all cases and in two (4.4%, 95% CI: 1.2%-14.5%) of the asymptomatic cases, the symptomatology worsened during hospital stay. Coinfections with both influenza and SARS-CoV-2 occurred in 35 patients (8.5% of all influenza positive patients). There was no difference in symptomatology between patients with co-infections and those with an influenza mono-infection. Patients could not be reliably categorized into carriers with low versus high viral loads based on symptomatology, age, and vaccination status. More than half of the influenza-positive individuals were either asymptomatic or had mild symptoms upon admission, while often carrying high viral loads. Our results show that without screening of patients at hospital admission, a considerable number of patients with a high viral load may be incorrectly classified as being not infectious.

Human papillomavirus (HPV) infections are prevalent skin infectious diseases. While there are no specific anti-HPV drugs available, understanding the viral mechanisms could lead to novel therapeutic strategies. Verruca vulgaris, a common HPV infection, is frequently encountered in dermatological clinics. The HPV E2 protein, an early viral protein, has been implicated in high-risk HPV infections by interacting with fibroblast growth factor receptor 3 (FGFR3) to inhibit viral DNA replication. However, the role of HPV E2 and FGFR3 in low-risk HPV infections remains elusive. Our study takes HPV2, a common subtype of verruca vulgaris, to explore the proliferation and immune regulatory effects of HPV2 E2 on keratinocytes. By overexpressing FGFR3 in HPV2 E2 stable expressing keratinocytes, we assessed changes in interferon-stimulated genes (ISGs) level and cell proliferation. Our findings revealed that HPV2 E2 induced phosphorylation of FGFR3 could activate JAK1-STAT1 pathway, thereby enhancing antiviral immunity through the upregulation of ISGs. Furthermore, we observed co-localization and interaction between FGFR3 and HPV2 E2 in keratinocytes. In conclusion, our study underscores the crucial role of FGFR3 in innate antiviral immunity against HPV2 infection in keratinocytes. These findings may provide a potential therapeutic target for HPV infections.

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 pandemic, has resulted in over 7 million confirmed deaths. In addition to severe respiratory and systematic symptoms, several comorbidities increase the risk of fatal outcomes. Therefore, it is essential to investigate the impact of COVID-19 on pre-existing conditions in patients, such as cancer and other infectious diseases. Recent clinical studies have reported the reactivation of human herpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV), in severe COVID-19 patients or vaccinated individuals. To support these clinical observations, we established a KSHV/SARS-CoV-2 co-infection system in A549-hACE2 cells. Our findings indicate that co-infection with live SARS-CoV-2 sharply induces KSHV lytic reactivation. Transcriptomic analysis revealed significant changes in global cellular gene expression in KSHV-infected A549-hACE2 cells, both with and without SARS-CoV-2 co-infection. These data provide a molecular basis for understanding whether patients with pre-existing oncogenic herpesvirus infections are at increased risk for more severe COVID-19 or for developing virus-associated cancers even after full recovery from COVID-19.

Kaposi's sarcoma-associated herpesvirus (KSHV) employs diverse mechanisms to subvert host immune responses, contributing to its infection and pathogenicity. As an immune evasion strategy, KSHV encodes the Membrane-Associated RING-CH (MARCH)-family E3 ligases, K3, and K5, which target and remove several immune regulators from the cell surface. In this study, we investigate the impact of K3 and K5 on lymphotoxin receptor (LTβR) ligands, LTβ and LIGHT, which are type II transmembrane proteins and function as pivotal immune mediators during virus infection. Upon co-expression of viral MARCH proteins with LTβR ligands, we showed that K3 and K5 selectively targeted LTβ, but not LIGHT, for the downregulation of surface expression. Specifically, K3 and K5 E3 ligases interacted with the transmembrane domain of LTβ. Intriguingly, K3 interacted with an immature form of LTβ, whereas K5 targeted the fully mature form. Subsequent biochemical analyses revealed that K3 disrupted the initial steps of N-glycosylation maturation of LTβ. This interference resulted in the sequestration of LTβ within the endoplasmic reticulum, impeding its trafficking to the plasma membrane. Consequently, the K3-mediated downregulation of LTβ surface expression suppressed the LTβR downstream signaling pathway. These findings uncover a novel mechanism by which KSHV K3 E3 ligase inhibits the membrane trafficking pathway of the LTβ inflammatory ligand through glycosylation interference, potentially evading LTβR-mediated antiviral immunity.

SARS-CoV-2 Envelope (E) protein is critical in viral assembly, release, and virulence. E gene was considered highly conserved and evolving slowly. Pan-sarbecoviruses-conserved regions in the E gene have been used as targets for various RT-PCR assays to detect SARS-CoV-2. It remains elusive whether SARS-CoV-2 variants of concern (VOCs) have accumulated significant E mutations that may affect protein stability and diagnostic RT-PCR assays. Herein we aimed to perform a comprehensive genetic analysis on the conservation and diversity of the E gene of SARS-CoV-2 and its VOCs in comparison with other human coronaviruses (HCoVs). In silico analysis of 20 326 HCoV E gene sequences retrieved from GenBank and GISAID suggests that SARS-CoV-2 E gene has multiple pan-HCoVs- and pan-SARS-CoV-2-conserved positions but accumulates significant mutations in VOC B.1.351 and Omicron strains. Mutations were often found in the 5' and 3' variable regions, whereas the central region is conserved. Nucleotide changes C109U and A114G may lead to potential failure of first-line SARS-CoV-2 diagnostic/screening assays. Nucleotide change C212U and its concomitant amino acid substitution Pro71Leu (i.e., C212U/Pro71Leu) is a hallmark mutation of B.1.351 variants, while C26U/Thr9Ile is characteristic of all Omicron variants. Later Omicron subvariants, such as XBB.1.5 and EG.5, additionally acquired the A31G/Thr11Ala mutation, as was confirmed by whole genome sequencing of SARS-CoV-2 in 118 pediatric cases. Wild-type E protein exhibits cytotoxicity to cells, but the mutations Thr9Ile, Thr11Ala, Thr9Ile + Thr11Ala, or Pro71Leu reduces its cytotoxicity. The Thr9Ile + Thr11Ala mutation stabilizes the E proteins of Omicron variants, while Pro71Leu alters the cellular distribution of the E protein, reducing its colocalization with the Golgi body. Altogether, this study not only sheds light on the conservation and diversity of the E gene in SARS-CoV-2 and its VOCs but also informs the improvement and development of SARS-CoV-2 or pan-HCoVs screening and diagnostic assays.