Structure of hepatitis E virion-sized particle reveals an RNA-dependent viral assembly pathway.
Hepatitis E virus (HEV) induces acute hepatitis in humans with a high fatality rate in pregnant women. There is a need for anti-HEV research to understand the assembly process of HEV native capsid. Here, we produced a large virion-sized and a small T=1 capsid by expressing the HEV capsid protein in insect cells with and without the N-terminal 111 residues, respectively, for comparative structural analysis. The virion-sized capsid demonstrates a T=3 icosahedral lattice and contains RNA fragment in contrast to the RNA-free T=1 capsid. However, both capsids shared common decameric organization. The in vitro assembly further demonstrated that HEV capsid protein had the intrinsic ability to form decameric intermediate. Our data suggest that RNA binding is the extrinsic factor essential for the assembly of HEV native capsids.
Xing
Li
L
From the Department of Molecular and Cellular Biology, University of California, Davis, California 95616; Structural Virology Section, Karolinska Institute, Huddinge University Hospital, SE-14186 Stockholm, Sweden.
Li
Tian-Cheng
TC
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Mayazaki
Naoyuki
N
From the Department of Molecular and Cellular Biology, University of California, Davis, California 95616; Structural Virology Section, Karolinska Institute, Huddinge University Hospital, SE-14186 Stockholm, Sweden.
Simon
Martha N
MN
Biology Department, Brookhaven National Laboratory, Upton, New York 11973-5000.
Wall
Joseph S
JS
Biology Department, Brookhaven National Laboratory, Upton, New York 11973-5000.
Moore
Mary
M
From the Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
Wang
Che-Yen
CY
From the Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
Takeda
Naokazu
N
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Wakita
Takaji
T
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Miyamura
Tatsuo
T
Department of Virology II, National Institute of Infectious Diseases, Tokyo 208-0011, Japan.
Cheng
R Holland
RH
From the Department of Molecular and Cellular Biology, University of California, Davis, California 95616. Electronic address: rhch@ucdavis.edu.
D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D016751:Hepatitis E / Q000401:mortality / Q000821:virology; D016752:Hepatitis E virus / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D009036:Moths; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000401:mortality / Q000821:virology; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly / Q000502:physiology*
D036022:Capsid Proteins; D012367:RNA, Viral