title: Mutational analysis of essential interactions involved in the assembly of hepatitis E virus capsid.
abstract: The hepatitis E virus (HEV) capsid consists of a single structural protein, a portion of which is engaged in isosahedral contact to form a basal shell, and another portion in dimeric contact to form the homodimers protruding from the shell. Previous studies revealed that homodimers of the truncated HEV capsid proteins, E2 (amino acids 394-606) and p239 (amino acids 368-606), model dominant antigenic determinants of HEV. Immunization with these proteins protected rhesus monkeys against the virus, and three monoclonal antibodies against the homodimers could neutralize HEV infectivity and/or immune-capture of the virus. Furthermore, homodimers of p239 further interact to form particles of 23 nm diameter, rendering it an efficacious candidate vaccine. In light of this we postulate that the interactions involved in the formation of the homodimers and particles might be similar to those involved in assembly of the virus capsid. Presently, mutational analysis was carried out to identify these sites of interactions. The site of dimeric interactions was located to a cluster of six hydrophobic amino acids residues, Ala597, Val598, Ala599, Leu601, and Ala602; furthermore, the site involved in particle formation was located at amino acids 368-394. The possibility that these sites are also involved in assembly of the virus capsid is supported by the fact that they are located at two major and highly conserved hydrophobic regions of the HEV structural protein.
authors.affiliation: Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen, 361005, China.
authors.forename: Shao-Wei
authors.initials: SW
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: He
authors.forename: Ying
authors.initials: Y
authors.lastname: Gu
authors.forename: Ru-Shi
authors.initials: RS
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Chen
authors.forename: Mun-Hon
authors.initials: MH
authors.lastname: Ng
authors.forename: Ning-Shao
authors.initials: NS
authors.lastname: Xia
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D004252:DNA Mutational Analysis; D019281:Dimerization; D016752:Hepatitis E virus / Q000235:genetics* / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D017434:Protein Structure, Tertiary; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D036022:Capsid Proteins