Genetic Variants in TNFSF4 and TNFSF8 Are Associated With the Risk of HCV Infection Among Chinese High-Risk Population

Abstract

BackgroundThe tumor necrosis factor superfamily (TNFSF) and TNF receptor superfamily (TNFRSF) play important roles in the immune responses to infections. The aim of this study was to determine the impact of single nucleotide polymorphisms (SNPs) of several TNFSF/TNFRSF genes on the risk of hepatitis C virus (HCV) infection in the Chinese high-risk population.MethodsThe TNFSF4-rs1234313, TNFSF4-rs7514229, TNFSF8-rs3181366, TNFSF8-rs2295800, TNFRSF8-rs2298209, and TNFRSF8-rs2230625 SNPs were genotyped in 2309 uninfected controls, 597 subjects with spontaneous HCV clearance and 784 patients with persistent HCV infection using the TaqMan-MGB assay. The putative functions of the positive SNPs were determined using online bioinformatics tools.ResultsAfter adjusting for gender, age, high-risk population, alanine transaminase (ALT), aspartate aminotransferase (AST), IL28B-rs12979860 and rs8099917 genotypes, the non-conditional logistic regression showed that rs7514229-T, rs3181366-T, and rs2295800-C were associated with an increased risk of HCV infection (all PFDR < 0.05). Combined analysis of rs7514229-T and rs3181366-T risk alleles showed that the subjects carrying 2–4 risk alleles were more susceptible to HCV infection compared with those lacking any risk allele (all P < 0.001). Furthermore, the risk of HCV infection increased with the number of risk alleles (Ptrend < 0.001). In silico analysis showed that rs7514229, rs3181366, and rs2295800 polymorphisms may affect the transcription of mRNA by regulating miRNA binding, TF binding, and promoter activation, respectively, which may have biological consequences.ConclusionTNFSF4-rs7514229, TNFSF8-rs3181366, and TNFSF8-rs2295800 are associated with increased risk of HCV infection in the Chinese high-risk population.

Transcriptional profiling specifies the pathogen-specific human host response to infectious keratitis

“…Similarly, neutrophils may also mediate tissue damage in trachomatous scarring, potentially through the production of reactive oxygen species and matrix metalloproteinases ( Barton et al., 2023 ). Some of the identified viral genes are also involved in other viral diseases, such as IKZF3 which promotes proliferation of HIV-1-infected cells ( Wei et al., 2023 ), IRF8 which is involved in the induction of downstream antiviral genes in monocytes by DNA viruses (such as HSV-1) but not RNA viruses ( Luo et al., 2022 ), and variants in TNFSF4 which are associated with the risk of HCV infection ( Fu et al., 2021 ). Thus, our results on human corneal tissue identify several mechanisms that are involved in the pathogenesis of viral infection and provide the foundation for a potential translation of previous findings from animal models to humans as novel therapeutic strategies for viral keratitis.…”

Single-cell RNA Sequencing Analysis Reveals New Immune Disorder Complexities in Hypersplenism

“…TNFSF8 was highly expressed in PH037 alone and was also enriched in CD4 + Naïve T-cells and CD4 + Treg cells ( Figures 2L, M ). Furthermore, previous research have found that TNFSF8 was associated with regulation of immune response ( 30 ) and high risk of hepatitis infection ( 31 ). In general, our research found that abnormal distribution and proportion of T-cells can be a characteristic of HS; these T-cell enriched functions and genes have certain characteristics, which are mainly manifested through immunosuppression.…”

The Endless Wars: Severe Fever With Thrombocytopenia Syndrome Virus, Host Immune and Genetic Factors

“…In this case, the possible influence of genetic background on SFTSV susceptibility, clinical manifestations, and outcomes was difficult to exclude, despite the underlying interpersonal transmission through contact with blood among family members. Moreover, the infections of a variety of viruses, such as hantavirus, dengue virus, influenza virus, and hepatitis C virus, had also been verified to correlate with genetic factors ( Xu-Yang et al., 2016 ; Kenney et al., 2017 ; Di Pucchio and Sekaly, 2020 ; Li Y. et al., 2020 ; Fu et al., 2021 ).…”