Welch Stephen R, Scholte Florine E M, Spengler Jessica R, Ritter Jana M, Coleman-McCray JoAnn D, Harmon Jessica R, Nichol Stuart T, Zaki Sherif R, Spiropoulou Christina F, Bergeron Eric
Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Microorganisms. 2020 May 21;8(5):775. doi: 10.3390/microorganisms8050775.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tri-segmented, tick-borne nairovirus that causes disease of ranging severity in humans. The CCHFV M segment encodes a complex glycoprotein precursor (GPC) that undergoes extensive endoproteolytic cleavage, giving rise to two structural proteins (Gn and Gc) required for virus attachment and entry, and to multiple non-structural proteins (NSm, GP160, GP85, and GP38). The functions of these non-structural proteins remain largely unclear. Here, we investigate the role of NSm during infection by generating a recombinant CCHFV lacking the complete NSm domain (10200∆NSm) and observing CCHFV ∆NSm replication in cell lines and pathogenicity in Ifnar mice. Our data demonstrate that the NSm domain is dispensable for viral replication in vitro, and, despite the delayed onset of clinical signs, CCHFV lacking this domain caused severe or lethal disease in infected mice.
克里米亚-刚果出血热病毒（CCHFV）是一种由蜱传播的、具有三个基因节段的内罗毕病毒，可导致人类出现不同严重程度的疾病。CCHFV的M基因节段编码一种复杂的糖蛋白前体（GPC），该前体经过广泛的内切蛋白酶切割，产生病毒附着和进入所需的两种结构蛋白（Gn和Gc），以及多种非结构蛋白（NSm、GP160、GP85和GP38）。这些非结构蛋白的功能在很大程度上仍不清楚。在此，我们通过构建一个缺失完整NSm结构域的重组CCHFV（10200∆NSm），并观察CCHFV∆NSm在细胞系中的复制情况以及在Ifnar小鼠中的致病性，来研究NSm在感染过程中的作用。我们的数据表明，NSm结构域对于病毒在体外的复制并非必需，并且，尽管临床症状出现延迟，但缺失该结构域的CCHFV在感染小鼠中仍会引发严重或致命疾病。
