口蹄疫病毒抑制宿主天然免疫应答研究进展

RECENT ADVANCES IN VIRAL IMMUNE SUPPRESSION MECHANISM OF FOOT-AND-MOUTH DISEASE VIRUS

口蹄疫病毒(Foot-and-mouth disease virus,FMDV)是引发猪、牛、羊等偶蹄类动物水泡病的病原。FMDV为小RNA病毒科、口蹄疫病毒属成员,基因组包含1个长的开放阅读框,其编码的多聚蛋白前体经过一系列切割和加工最终形成4种结构蛋白和10种非结构蛋白。FMDV感染宿主能够引发显著的免疫抑制。FMDV对天然免疫应答的抑制是早期感染过程中病毒能够快速复制的一个重要原因,而FMDV的多个结构蛋白和非结构蛋白已被证实参与了对天然免疫信号通路活化的抑制。FMDV蛋白水解酶Lpro和3Cpro是最早被发现的具有免疫抑制功能的病毒蛋白。近年来,随着FMDV的其他蛋白也被发现具有免疫抑制功能,一些新的免疫抑制和免疫逃逸机制不断被解析。本文对目前已报道的FMDV蛋白抑制天然免疫应答的机制进行综述,希望为FMDV致病机制的进一步阐明提供理论依据,同时也为口蹄疫基因工程疫苗的改造提供思路和参考。

Foot-and-mouth disease virus(FMDV)is the causative agent of a vesicular disease that affects pigs,cattle,sheep and other cloven-hoofed animals.FMDV belongs to the genus Aphthovirus in the Picornaviridae family.The viral genome is about 8.5 kb in length that includes an open reading frame(ORF).The single long ORF encodes a polyprotein that is finally processed into four mature structural proteins and ten non-structural proteins.FMDV infection results in significant immune suppression.The suppression of innate immune response is responsible for the rapid viral replication at the early infection in hosts.Both the structural and non-structural proteins of FMDV have been found to participate in suppression of innate immune pathway signaling.FMDV proteases Lpro and 3Cpro are the most well-known viral proteins that possess suppressive effect on host innate immune responses.In addition,other viral proteins have been recently found to possess the function in suppression of host innate immune signaling and some new immune suppression or evasion strategies have been uncovered.Here,we review the recent advances in viral immune suppression mechanisms of FMDV,which may help better clarify the pathogenesis of FMDV infection and provide insights into development and improvement of genetically engineered vaccines.