Abstract
The hepatitis E virus (HEV) is a causative agent of hepatitis E. HEV virions in circulating blood and culture media are quasi-enveloped, while those in feces are nonenveloped. The capsid (ORF2) protein associated with an enveloped HEV virion is reported to comprise the translation product of leucine 14/methionine 16 to 660 (C-terminal end). However, the nature of the ORF2 protein associated with fecal HEV remains unclear. In the present study, we compared the molecular size of the ORF2 protein among fecal HEV, cell-culture-generated HEV (HEVcc), and detergent-treated protease-digested HEVcc. The ORF2 proteins associated with fecal HEV were C-terminally truncated and showed the same size as those of the detergent-treated protease-digested HEVcc virions (60 kDa), in contrast to those of the HEVcc (68 kDa). The structure prediction of the ORF2 protein (in line with previous studies) demonstrated that the C-terminal region (54 amino acids) of an ORF2 protein is in flux, suggesting that proteases target this region. The nonenveloped nondigested HEV structure prediction indicates that the C-terminal region of the ORF2 protein moves to the surface of the virion and is unnecessary for HEV infection. Our findings clarify the maturation of nonenveloped HEV and will be useful for studies on the HEV lifecycle.
Highlights
Introduction iationsHepatitis E is acute hepatitis, a generally self-limiting and rarely fatal disease, with a lethality of 0.5–3% among young adults; this rate reaches 20–30% in pregnant women [1,2]
When subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDSPAGE) and immunoblotting, the secreted glycosylated ORF2 proteins and the virionassociated ORF2 proteins in the culture supernatant of the genotype 3b hepatitis E virus (HEV) (JE03-1760F)producing PLC/PRF/5 cells were detected in approximately 80- and 68-kDa forms, respectively (Figure 1), consistent with previous reports [20,26]
Other studies digestion in the HEV virion occurs at the C-terminal region of the ORF2 protein, we report that the C-terminal regions of the ORF2 proteins were located at the surface of virus-like particle (VLP)
Summary
Hepatitis E is acute hepatitis, a generally self-limiting and rarely fatal disease, with a lethality of 0.5–3% among young adults; this rate reaches 20–30% in pregnant women [1,2]. This form of hepatitis is caused by hepatitis E virus (HEV) infection via the fecal–oral route, from polluted water in developing countries [1,2]. HEV belongs to the Hepeviridae family, which is classified into two genera: Orthohepevirus and Piscihepevirus [8]. The genus, Orthohepevirus, is divided into four species (A–D). The Orthohepevirus A species includes eight different HEV genotypes (1–8).
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