Abstract
Hepatitis E virus (HEV), a non-enveloped, positive-stranded RNA virus, is transmitted in a faecal-oral manner, and causes acute liver diseases in humans. The HEV capsid is made up of capsomeres consisting of homodimers of a single structural capsid protein forming the virus shell. These dimers are believed to protrude from the viral surface and to interact with host cells to initiate infection. To date, no structural information is available for any of the HEV proteins. Here, we report for the first time the crystal structure of the HEV capsid protein domain E2s, a protruding domain, together with functional studies to illustrate that this domain forms a tight homodimer and that this dimerization is essential for HEV–host interactions. In addition, we also show that the neutralizing antibody recognition site of HEV is located on the E2s domain. Our study will aid in the development of vaccines and, subsequently, specific inhibitors for HEV.
Highlights
Infectious viral hepatitis is a major health problem in both developing and developed countries
Virus (HEV) capsid was solved by the Single-wavelength Anomalous Dispersion (SAD) method from a synchrotron data set using Br heavy atom soaked crystals
Hepatitis E virus (HEV) antibody recognition and E2s We have investigated the functional relevance of E2 constructs through a panel of 33 previously reported mAb that are reactive against the E2 fragment and p239 (Table S1)
Summary
Infectious viral hepatitis is a major health problem in both developing and developed countries. Sequence comparisons and phylogenetic taxonomy differentiate HEV from Calicivirus, and it defines a new family named Hepeviridae [2,3]. A 22 Alow- resolution cryoEM structure of recombinant HEV viruslike particles shows that the virus capsid is made up of subunits (capsomeres) consisting of homodimers of this structural protein [5]. Subunits of this dimeric capsid protein interact through their dimeric C-terminal domain to form a virus shell that protrudes from the viral surface [5,6]. The initial contact with host cells to initiate viral infection is believed to occur through these protrusions [7]
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