一种新颖Potyviridae病毒编码特异串联的前导半胱氨酸蛋白酶（HCPro1-HCPro2）协同调控寄主适应性的新机制研究

Potyviridae是第一大植物RNA病毒科，该科病毒基因组N端编码的前导蛋白酶高度变异，被赋予重要的生物学意义。此科成员数量最多的Potyvirus病毒编码前导丝氨酸蛋白酶和半胱氨酸蛋白酶（P1-HCPro），P1通过自身顺式切割精确调控HCPro的基因沉默抑制子（RSS）活性、维护病毒的寄主适应性。课题组前期从海南槟榔中鉴定出新颖病毒-ANSSV，编码特异串联的前导半胱氨酸蛋白酶（HCPro1-HCPro2）。不同于P1-HCPro类型，HCPro2的RSS活性不受前置蛋白酶-HCPro1的顺式切割影响。但HCPro1促进HCPro2发生蛋白水平的下调表达，且HCPro1发生自噬降解，推测HCPro1介导的自噬调控HCPro2的表达、维护寄主适应性。本课题旨在探究HCPro1操纵自噬调控RSS蛋白表达的分子机理，阐明病毒的寄主适应性新机制，为设计新颖的病毒病害防控策略提供理论依据。

Potyviridae is the largest family of plant-infecting RNA viruses. The leader proteases encoded by potyvirids vary greatly, and are endowed with important biological significance. Potyviruses, the most virus species of the family Potyviridae, encode the leader serine protease and cysteine protease (P1-HCPro). P1’s self-cleavage in cis elaborately modulates RNA silencing suppressor (RSS) activity of HCPro, maintaining viral host adaption. Previously, we identified a novel potyvirid from areca palm in Hainan, which was referred to as areca palm necrotic spindle-spot virus (ANSSV). We demonstrated that the genomic N-terminus of ANSSV encodes the unique leader cysteinases (HCPro1 and HCPro2 in tandem). Different from that of P1-HCPro type, the RSS activity of HCPro2 was not influenced by the cis-cleavage activity of its proceeding protease - HCPro1. However, HCPro1 promotes the down-regulation expression of HCPro2 protein, as well as HCPro1 is degraded by cellular autophagy machinery, implying that HCPro1-mediated autophagic degradation regulate the expression of HCPro2 and maintain viral host fitness. In this study, we aim to investigate the molecular mechanism that HCPro1 manipulates autophagy machinery to regulate the expression of RSS protein - HCPro2, and elucidate a novel mechanism of viral host adaption, which will provide theoretical basis for designing novel strategies for viral disease control.