分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Wang, Xiangxi
Gao, Qiang
Sun, Yao
Li, Xuemei
Rao, Zihe
Ren, Jingshan
Stuart, David I.
Fry, Elizabeth E.
Gao, Qiang
Yin, Weidong
Hu, Zhongyu
Wang, Junzhi
Rowlands, David J.
Rowlands, David J.
Stuart, David I.
Rao, Zihe
Rao, Zihe
摘要： Hepatitis A virus(HAV) remains enigmatic, despite 1.4 million cases worldwide annually(1). It differs radically from other picornaviruses, existing in an enveloped form(2) and being unusually stable, both genetically and physically(3), but has proved difficult to study. Here we report high-resolution X-ray structures for the mature virus and the empty particle. The structures of the two particles are indistinguishable, apart from some disorder on the inside of the empty particle. The full virus contains the small viral protein VP4, whereas the empty particle harbours only the uncleaved precursor, VP0. The smooth particle surface is devoid of depressions that might correspond to receptor-binding sites. Peptide scanning data extend the previously reported VP3 antigenic site4, while structure-based predictions(5) suggest further epitopes. HAV contains no pocket factor and can withstand remarkably high temperature and low pH, and empty particles are even more robust than full particles. The virus probably uncoats via a novel mechanism, being assembled differently to other picornaviruses. It utilizes a VP2 'domain swap' characteristic of insect picorna-like viruses(6,7), and structure-based phylogenetic analysis places HAV between typical picornaviruses and the insect viruses. The enigmatic properties of HAV may reflect its position as a link between 'modern' picornaviruses and the more 'primitive' precursor insect viruses; for instance, HAV retains the ability to move from cell-to-cell by transcytosis(8,9).
分类： 生物学 >> 生物物理学 提交时间： 2016-05-05
Guo, Yu
Ma, Chao
Wang, Xu
Wang, Xin
Liu, Pi
Lin, Jianping
Guo, Yu
Ma, Chao
Wang, Xu
Wang, Xin
Liu, Pi
Lin, Jianping
Lou, Zhiyong
Lou, Zhiyong
Sun, Yuna
Lou, Zhiyong
Shen, Shu
Deng, Fei
Wang, Hualin
Wang, Wenming
摘要： Hantaviruses, which belong to the genus Hantavirus in the family Bunyaviridae, infect mammals, including humans, causing either hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS) in humans with high mortality. Hantavirus encodes a nucleocapsid protein (NP) to encapsidate the genome and form a ribonucleoprotein complex (RNP) together with viral polymerase. Here, we report the crystal structure of the core domains of NP (NPcore) encoded by Sin Nombre virus (SNV) and Andes virus (ANDV), which are two representative members that cause HCPS in the New World. The constructs of SNV and ANDV NPcore exclude the N- and C-terminal portions of full polypeptide to obtain stable proteins for crystallographic study. The structure features an N lobe and a C lobe to clamp RNA-binding crevice and exhibits two protruding extensions in both lobes. The positively charged residues located in the RNA-binding crevice play a key role in RNA binding and virus replication. We further demonstrated that the C-terminal helix and the linker region connecting the N-terminal coiled-coil domain and NPcore are essential for hantavirus NP oligomerization through contacts made with two adjacent protomers. Moreover, electron microscopy (EM) visualization of native RNPs extracted from the virions revealed that a monomer-sized NP-RNA complex is the building block of viral RNP. This work provides insight into the formation of hantavirus RNP and provides an understanding of the evolutionary connections that exist among bunyaviruses. IMPORTANCE Hantaviruses are distributed across a wide and increasing range of host reservoirs throughout the world. In particular, hantaviruses can be transmitted via aerosols of rodent excreta to humans or from human to human and cause HFRS and HCPS, with mortalities of 15% and 50%, respectively. Hantavirus is therefore listed as a category C pathogen. Hantavirus encodes an NP that plays essential roles both in RNP formation and in multiple biological functions. NP is also the exclusiv
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