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Review
. 2019 Sep 20;11(10):883.
doi: 10.3390/v11100883.

Hepatitis E Virus Entry

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Free PMC article
Review

Hepatitis E Virus Entry

Xin Yin et al. Viruses. .
Free PMC article

Abstract

Hepatitis E virus (HEV) infection is a major cause of acute hepatitis worldwide. It is transmitted enterically but replicates in the liver. Recent studies indicate that HEV exists in two forms: naked, nonenveloped virions that are shed into feces to mediate inter-host transmission, and membrane-cloaked, quasienveloped virions that circulate in the bloodstream to mediate virus spread within a host. Both virion types are infectious, but differ in the way they infect cells. Elucidating the entry mechanism for both virion types is essential to understand HEV biology and pathogenesis, and is relevant to the development of treatments and preventions for HEV. This review summarizes the current understanding of the cell entry mechanism for these two HEV virion types.

Keywords: NPC1; lysosomal acid lipase; quasienveloped virus; receptor.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The hepatitis E virus (HEV) genome, its encoded proteins (a), and two types of virions (b).
Figure 2
Figure 2
Model for cellular entry of naked and quasi-enveloped HEV virions. Naked HEV virions initially bind nonspecifically to HSPGs, followed by a specific interaction with a putative cell receptor. Receptor binding triggers virion internalization via clathrin-mediated endocytosis and virions subsequently uncoat in a Rab5− early endocytic compartment. Quasienveloped HEV virions attach to cells less efficiently than naked virions, but are similarly internalized via clathrin-mediated endocytosis. Virions are routed through early (Rab5+) and late (Rab7+) endocytic compartments and ultimately reach the lysosome. The quasi-envelope becomes slowly degraded by lysosomal enzymes, allowing the exposure of the capsid which subsequently penetrates the endosomal membrane to release its genome into the cytoplasm.

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