Formation of Genetically Determined Resistance against Human Norovirus Infection through Polymorphism of the FUT2 gene: a Review of the Literature

R. O. Bykov, A. V. Semenov, P. K. Starikova, T. M. Itani
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Abstract

Relevance. Human Noroviruses (HuNoV) are highly contagious pathogens responsible of acute human norovirus infection. HuNoV is the cause of every fifth case of acute non-bacterial gastroenteritis, annually causing about 699 million cases of the disease and more than 200 thousand deaths worldwide. Controlled expression of the HBGA antigens by the FUT2 gene causes resistance to human norovirus. Polymorphisms of the FUT family genes contribute to partial or complete immunity to certain genogroups/ genotypes of norovirus.Aims. To characterize the effect of FUT2 gene polymorphisms on susceptibility to HuNoV.Results. Nonsensemutations of G428A in two homologous alleles contribute to the formation of a secretory-negative phenotype (se), which is a factor determining immunity to noroviruses. Some missense-mutations in the nucleotide positions se385,571 form partial resistance against certain genotypes. People with a secretory-negative phenotype are immune to infection by the GII.4 genotype and its genovariants.Conclusions. The expression of HLA antigens by the functionally inactive FUT2 gene plays a key role in the resistance of the human population to HuNoV. Susceptibility to HuNoV largely depends on the prevalence of HBGA phenotypic diversity among ethnic populations around the world. Targeted screening aimed at identifying polymorphisms of the FUT family will allow identifying risk groups more susceptible to HuNoV.
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通过 FUT2 基因的多态性形成由基因决定的对人类诺瓦克病毒感染的抵抗力:文献综述
相关性。人类诺如病毒(HuNoV)是造成急性人类诺如病毒感染的高度传染性病原体。每五例急性非细菌性肠胃炎病例中就有一例是由 HuNoV 引起的,每年在全球造成约 6.99 亿例病例和 20 多万人死亡。FUT2 基因对 HBGA 抗原的控制表达导致了对人类诺如病毒的抵抗力。FUT 家族基因的多态性可导致对某些诺如病毒基因群/基因型的部分或完全免疫。研究 FUT2 基因多态性对诺如病毒易感性的影响。两个同源等位基因中 G428A 的无义突变导致分泌阴性表型(se)的形成,而分泌阴性表型是决定对诺如病毒免疫力的一个因素。se385、571等核苷酸位置上的一些错义突变形成了对某些基因型的部分抵抗力。具有分泌阴性表型的人对 GII.4 基因型及其基因变异体的感染具有免疫力。功能不活跃的 FUT2 基因对 HLA 抗原的表达在人类对 HuNoV 的抵抗力中起着关键作用。对 HuNoV 的易感性在很大程度上取决于 HBGA 表型多样性在世界各地种族人群中的流行程度。旨在确定 FUT 家族多态性的定向筛查将有助于确定对 HuNoV 更易感的风险群体。
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