SARS样冠状病毒特有基因orfX的功能研究

SARS冠状病毒（SARS-CoV）引起严重急性呼吸综合症，而蝙蝠携带遗传多样的SARS样冠状病毒（SL-CoVs），被认为是SARS-CoV的自然宿主。近期我们在菊头蝠发现了一类更接近SARS-CoV的病毒，并首次成功分离到一株与SARS病毒高度同源的SL-CoV（WIV1）。证实WIV1同SARS-CoV一样，利用受体ACE2入侵细胞，能感染人、猪、猴、蝙蝠等多种哺乳动物细胞，显示其宿主范围广泛。WIV1和SARS-CoV基因组结构最大的不同在于其特有的orfX基因，编码一个约9kD的蛋白，初步实验显示ORFX是一个有功能的蛋白，在人细胞系中可以抑制I型干扰素生成，推测其功能与病毒致病性相关。本研究将进一步分析ORFX蛋白在感染细胞中的定位、对病毒复制的影响以及调节人类干扰素应答的机制，揭示ORFX蛋白对病毒增殖和致病能力的影响，为后续更深入研究SL-CoV致病机理提供基础。

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the causative agent of the 2002-03 SARS pandemic. In our previous studies, we have discovered genetically diverse SARS-like coronaviruses (SL-CoVs) from Chinese horseshoe bats and isolated one SL-CoV (WIV1) that has a higher similarity with the SARS-CoV in genomic sequences, and uses the same receptor, ACE2, as the SARS-CoV. Our results further demonstrated that Chinese horseshoe bats are natural reservoirs of the SARS-CoV. Cell susceptibility experiment indicated demonstrated that WIV1 can infect cell lines derived from human, pig, monkey, and bat, indicating WIV1 has a broad host range. However, compared with the SARS-CoV, the WIV1 has an additional unique open reading frame X (orfX). Preliminary experiments showed that orfX is a functional protein and can inhibit type I interferon in human cells. In this project, we will further investigate it’s function through cellular localization, regulation of type I interferon response and effect on virus replication. The expected results will be helpful for understanding of the pathogenesis of WIV1.