Figure 1 Negative contrast electron micrograph of virions of an isolate of hepatitis E virus, in the bile fluid from a monkey challenged with the genotype 2 Mexican strain of hepatitis E virus. The bar represents 100 nm.
(From Ticehurst et al. (1992). J. Infect. Dis., 165, 835–845; with permission.)
Figure 2 Structure of the hepatitis E virus-like particle (VLP) (T=1). (A) Crystal structure of hepatitis E virus VLP. The three domains, S, P1 and P2 are colored blue, yellow and red, respectively. The VLP is positioned in a standard orientation with the 3 2-fold icosahedral symmetry axes aligned along the vertical, horizontal, and viewing directions, respectively. (B) Cryo-EM reconstruction at 14 Å resolution. The surface is colored by radial depth cue from blue, yellow, to red. (C) Hepatitis E virus VLP with only the S domain. (D) VLP with S and P1 domains. (E) VLP with P1 and P2 domains.
(From Guu et al. (2009). Proc. Natl Acad. Sci., U S A, 106, 12992–12997; with permission.)
Figure 3 Electron micrograph of 30–35 nm diameter particles of Avian hepatitis E virus. The virus particles were detected from a bile sample of a chicken with hepatitis–splenomegaly syndrome. Bar=100 nm.
(From Haqshenas et al. (2001). J. Gen. Virol., 82, 2449–2462; with permission.)
Figure 4 Schematic diagram of the genomic organization of hepatitis E virus: a short 5′ non-coding region (NCR), a 3′ NCR, and three ORFs. ORF2 and ORF3 overlap each other but neither overlaps ORF1. ORF1 encodes non-structural proteins including putative functional domains; ORF2 encodes capsid protein and ORF3 encodes a small phosphoprotein with a multi-functional C-terminal region. MT, methytransferase; Y, “Y” domain; P, a papain-like cystein protease; HVR, a hypervariable region that is dispensable for virus infectivity; Hel, helicase; RdRp, RNA-dependent RNA polymerase
(From Meng, X.J. (2008). Hepatitis E virus (Hepevirus). In: Encyclopedia of Virology (5 vols), 3rd edn (B.W.J. Mahy and M.H.V. van Regenmortel, Eds.), Oxford, Elsevier, pp. 377–383; with permission.)
Figure 5 Phylogenetic trees depicting the relationship between strains of mammalian hepatitis E virus in the genus Hepevirus and the unassigned species Avian hepatitis E virus (courtesy of Hiroaki Okamoto). (A) A phylogenetic tree based on the full-length genomic sequences of representative hepatitis E virus strains including the four major genotypes of mammalian hepatitis E virus, the newly-identified rabbit hepatitis E virus and the three genotypes of Avian hepatitis E virus; (B) A phylogenetic tree based upon partial sequence (1545 nt) of the rat hepatitis E virus along with other hepatitis E virus strains in Figure 6A. GenBank accession numbers for the strains used in these analyses are Burma hHEV (M73218); Morocco hHEV (AY230202); Mexico hHEV (M74506); USA hHEV (AF060669); USA sHEV (AF082843); Japan gt3-hHEV1 (AP003430); Japan gt3-sHEV (AB073912); Japan gt3-hHEV2 (AB248520); Kyrgyzstan sHEV (AF455784); China hHEV (AJ272108); Japan gt4-sHEV (AB097811); Japan gt4-hHEV (AB220973); USAaHEV (AY535004); aavUSAaHEV (EF206691); AaHEV (AM943647); EaHEV (AM943646); rabbit HEV1 (FJ906895); rabbit HEV2 (FJ906896); rat HEV1 (GQ504009); and rat HEV2 (GQ504010).
Figure 6 Phylogenetic relationships of hepatitis E virus with members of the families Picornaviridae, Caliciviridae and Togaviridae. The helicase (Hel) and polymerase (Pol) regions of the genome were analyzed (courtesy of T. Berke and D.O. Matson). (A) Partial gene sequences (200 aa) from the proposed helicase region were used for the phylogenetic analysis and included representative strains from each family. Clustal W v1.7 was used to create a multiple alignment for the aa sequences, which was verified by alignment of known motifs in the region (e.g. GxGKS/T). The nt sequences were added and aligned by hand using the corresponding aa sequences as a template resulting in a consensus length of 608 nt. A phylogenetic tree was constructed from the nt sequence alignment using the maximum likelihood algorithm in the program DNAML from the PHYLIP 3.52c package within UNIX environment. For the algorithm, the global rearrangement option was invoked and the order of sequence input was randomized ten times. Other menu options were left as default. The resultant tree is unrooted and the phylogenetic distances are in the unit of expected number of substitutions per site. Branch points of the resulting tree had a confidence level of P<0.01 (P<0.05*). GenBank accession numbers for the strains in this analysis were M87661 (Norwalk virus, NLV-NV68), X86557 (Lordsdale virus, NLV-LD93), U52086 (primate calicivirus, VESV-Pan1), U13992 (feline calicivirus, FCV-CFI/68), Z69620 (European brown hare syndrome virus, EBHV-GD), M67473 (rabbit hemorrhagic disease virus, RHDV-GH), X86560 (Sapporo virus, SLV-Man93), J02281 (human poliovirus 1, PV-1), K02121 (Human rhinovirus type 14, HRV-14), M22458 (encephalomyocarditis virus, EMCV), X00429 (foot-and-mouth disease virus, FMDV), K02990 (hepatitis A virus, HAV), M15240 (rubella virus), J02363 (Sindbis virus), M73218 (hepatitis E virus, HEV-Burma), M80581 (hepatitis E virus, HEV-Sar55), M74506 (hepatitis E virus, HEV-Mexico), AF011921 (hepatitis E virus, HEV-Swine). (B) Partial gene sequences (200 aa) from the proposed polymerase region were used for the phylogenetic analysis and included representative strains from each family. Clustal W v1.7 was used to create a multiple alignment for the aa sequences, which was verified by alignment of known motifs in the region (e.g. SGxxxTxxxMT/S, GDD). The nt sequences were added and aligned by hand using the corresponding aa sequences as template resulting in a consensus length of 590 nt. A phylogenetic tree was constructed as described above and GenBank accession numbers for the strains in this analysis were identical to those above.