Molecular basis for the formation of ribonucleoprotein complex of Crimean-Congo hemorrhagic fever virus

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• 作者：Xiaojing Wang^a ; ¹ ; Baobin Li^b ; ^g ; ¹ ; Yu Guo^c ; ^d ; Shu Shen^e ; Liang Zhao^a ; Peisheng Zhang^b ; Yuna Sun^d ; Sen-Fang Sui^a ; ^{suisf@mail.tsinghua.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Fei Deng^e ; ^{df@wh.iov.cn" class="auth_mail" title="E-mail the corresponding author} ; Zhiyong Lou^b ; ^c ; ^f ; ^{louzy@mail.tsinghua.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：CCHFV ; Crimean-Congo hemorrhagic fever virus
• 刊名：Journal of Structural Biology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：196
• 期：3
• 页码：455-465
• 全文大小：2285 K

文摘

Negative-sense single-strand RNA (-ssRNA) viruses comprise a large family of pathogens that cause severe human infectious diseases. All -ssRNA viruses encode a nucleocapsid protein (NP) to encapsidate the viral genome, which, together with polymerase, forms a ribonucleoprotein complex (RNP) that is packaged into virions and acts as the template for viral replication and transcription. In our previous work, we solved the monomeric structure of NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV), which belongs to the Nairovirus genus within the Bunyaviridae family, and revealed its unusual endonuclease activity. However, the mechanism of CCHFV RNP formation remains unclear, due to the difficulty in reconstructing the oligomeric CCHFV NP-RNA complex. Here, we identified and isolated the oligomeric CCHFV NP-RNA complex that formed in expression cells. Sequencing of RNA extracted from the complex revealed sequence specificity and suggested a potential encapsidation signal facilitating the association between NP and viral genome. A cryo-EM reconstruction revealed the ring-shaped architecture of the CCHFV NP-RNA oligomer, thus defining the interaction between the head and stalk domains that results in NP multimerization. This structure also suggested a modified gating mechanism for viral genome encapsidation, in which both the head and stalk domains participate in RNA binding. This work provides insight into the distinct mechanism underlying CCHFV RNP formation compared to other -ssRNA viruses.