Alteration of Antiviral Signalling by Single Nucleotide Polymorphisms (SNPs) of Mitochondrial Antiviral Signalling Protein (MAVS)

Abstract

Genetic variation is associated with diseases. As a type of genetic variation occurring with certain regularity and frequency, the single nucleotide polymorphism (SNP) is attracting more and more attention because of its great value for research and real-life application. Mitochondrial antiviral signalling protein (MAVS) acts as a common adaptor molecule for retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), which can recognize foreign RNA, including viral RNA, leading to the induction of type I interferons (IFNs). Therefore, MAVS is thought to be a crucial molecule in antiviral innate immunity. We speculated that genetic variation of MAVS may result in susceptibility to infectious diseases. To assess the risk of viral infection based on MAVS variation, we tested the effects of twelve non-synonymous MAVS coding-region SNPs from the National Center for Biotechnology Information (NCBI) database that result in amino acid substitutions. We found that five of these SNPs exhibited functional alterations. Additionally, four resulted in an inhibitory immune response, and one had the opposite effect. In total, 1,032 human genomic samples obtained from a mass examination were genotyped at these five SNPs. However, no homozygous or heterozygous variation was detected. We hypothesized that these five SNPs are not present in the Japanese population and that such MAVS variations may result in serious immune diseases.

The Absence of Interferon-β Promotor Stimulator-1 (IPS-1) Predisposes to Bronchiolitis and Asthma-like Pathology in Response to Pneumoviral Infection in Mice

“…Polymorphisms at the IPS1 locus are linked to type-I IFN deficiency in man and may therefore underlie susceptibility to viral infections 16 . Here, we questioned whether an interaction between IPS-1 deficiency and respiratory viral infection might underpin the association between attenuated IFN responses, severe bronchiolitis and subsequent development of asthma.…”

Bone Marrow–Derived Mesenchymal Stem Cells From Patients With Systemic Lupus Erythematosus Have a Senescence‐Associated Secretory Phenotype Mediated by a Mitochondrial Antiviral Signaling Protein–Interferon‐β Feedback Loop

“…It has been reported that the C79F MAVS SNP leads to a MAVS loss-of-function mutation by impairing MAVS-tumor necrosis factor receptor-associated factor 3 interaction, Female Female Female Female Female Female Passage 2 2 2 2 2 2 Total SLEDAI score 6 6 2 7 0 2 Anti-RNP, AI (normal 0.0-0.9) and this mutation is more frequent in individuals of African origin (32). Therefore, the genomic samples from SLE patients were genotyped at the rs11905552 site in the MAVS gene for the C79F MAVS SNP (29). No C79F MAVS SNP was found in the SLE patients in this study (data not shown), ruling out the possibility that the MAVS loss-of-function mutation could have contributed to the phenotypes observed in the present work.…”

Interaction Between Susceptibility Loci in MAVS and TRAF3 Genes, and High-risk HPV Infection on the Risk of Cervical Precancerous Lesions in Chinese Population

“…We found that the heterozygous genotype (CA) in MAVS rs6052130 was significantly associated with an increased risk of cervical precancerous lesions. Previous studies have confirmed that SNPs in MAVS exerted inhibitory effects on antiviral signaling in response to dsRNA (42). In addition, Lad and colleagues (43) found the splicing variants of MAVS, MAVS 1a, inhibits RIG-I and MAVS activity.…”

“…Our functional analysis in PBMCs showed that the MAVS rs6052130 CA or AA genotype might downregulate the production of IFNb, although a significant difference of MAVS mRNA expression in different rs6052130 genotypes was not observed. Therefore, we speculated that the rs6052130 variant in the MAVS gene might contribute to dislocation of MAVS from the outer mitochondria membrane (42), which may lead to loss of RLR antiviral signaling in response to HPV, thereby promoting evasion of HPV, leading to a more robust infection and ultimately contributing to an increased risk of cervical precancerous lesions. More studies are warranted to elucidate these speculations.…”