Molecular Biology and Infection of Hepatitis E Virus

Abstract

Hepatitis E virus (HEV) is a viral pathogen transmitted primarily via fecal-oral route. In humans, HEV mainly causes acute hepatitis and is responsible for large outbreaks of hepatitis across the world. The case fatality rate of HEV-induced hepatitis ranges from 0.5 to 3% in young adults and up to 30% in infected pregnant women. HEV strains infecting humans are classified into four genotypes. HEV strains from genotypes 3 and 4 are zoonotic, whereas those from genotypes 1 and 2 have no known animal reservoirs. Recently, notable progress has been accomplished for better understanding of HEV biology and infection, such as chronic HEV infection, in vitro cell culture system, quasi-enveloped HEV virions, functions of the HEV proteins, mechanism of HEV antagonizing host innate immunity, HEV pathogenesis and vaccine development. However, further investigation on the cross-species HEV infection, host tropism, vaccine efficacy, and HEV-specific antiviral strategy is still needed. This review mainly focuses on molecular biology and infection of HEV and offers perspective new insight of this enigmatic virus.

Keywords: HEV; HEV biology; HEV infection; HEV vaccine; hepatitis E virus; viral proteins of HEV.

FIGURE 1

Schematic illustration of hepatitis E virus (HEV) genome, subgenomic RNA, and ORFs. ORF1 (nt 26–5107) is labeled above the genomic RNA box. ORF2 (nt 5145–7127) and ORF3 (nt 5131–5475) are encoded by the same subgenomic RNA. The newly identified ISRE like sequence (nt 2701–2787) and ORF4 (nt 2835–3308) which are overlapped with ORF1 are listed as well. Moreover, the numbers above or below the RNA boxes indicate nucleotide numbers of the cDNA of HEV Sar55 (GenBank accession number AF444002) genomic RNA.

FIGURE 2

Schematic illustration of putative domains in ORF1 polyprotein. Met: Methyltransferase domain; Y: Y domain; PCP: papain-like cysteine protease; HV: hypervariable region; Pro: proline-rich domain; X: X-domain; Hel: helicase; RdRp: RNA-dependent RNA polymerase. The numbers above the box indicate amino acid residues of ORF1-encoded polyprotein of Sar55 strain.

FIGURE 3

Schematic illustration of the domains of the HEV capsid protein encoded by ORF2. The numbers above the box and those in parentheses indicate amino acid residues of the capsid protein. S domain: shell domain; M domain: middle domain; P domain: protruding Domain.