Detection and molecular characterization of hepatitis E virus in clinical, environmental and putative animal sources.

Arch Virol. 2012 Dec;157(12):2363-8.

Ishida S, Yoshizumi S, Ikeda T, Miyoshi M, Goto A, Matsubayashi K, Ikeda H.

Department of Infectious Diseases, Hokkaido Institute of Public Health, North 19, West 12, Kita-ku, Sapporo 060-0819, Japan.



Putative animal reservoirs and environmental samples were studied to investigate potential routes of transmission for indigenous hepatitis E virus (HEV) infection in Hokkaido, Japan. A total of 468 liver samples and 954 environmental samples were collected from 2003 to 2011 for this study. Four swine livers (1 %) were positive for HEV RNA; two strains belonged to genotype 3 and the other two strains were genotype 4. Genotype 3 HEV was detected in a sewage sample and a seawater sample. HEV strains derived from swine liver, seawater and raw sewage samples shared 93-100 % sequence similarity with human HEV strains.

PMID: 22847755


Supplementary information:

The sampling sites in Hokkaido, the region of Japan, were grouped into four regions in our previous report to investigate the relationship between genetic diversity of HEVs and their geographical distribution: E, S, C and N. Eight strains from clinical samples that were collected between December in 2011 and February in 2012 in the same C region showed clustering with high similarity approximately 99-100% identity (Fig.1). In addition, these HEV strains were closely related to strains those were detected successively from 11 patients in the C region in 2009 (Ozeki I et al., 2012, reported in Japanese). This finding indicates that an HEV strain may have had a common infection source in this area. Initially, food items were suspected as the source in these cases. However, neither a common infection source nor event for epidemic could be identified.

HEV infection is generally subclinical during the 6 weeks or so following primary infection even in individuals who develop the illness. Most HEV-infected cases recover spontaneously without developing obvious hepatitis or even any symptoms. Additionally, the period possible to detect the viral gene from clinical samples is limited to only the acute phase. Therefore, it is generally difficult to identify the source of infection and trace the route of infection. Phylogenetic analysis and detailed epidemiological investigation seem to be important and helpful for distinguishing cluster cases from sporadic ones. More sensitive and specific methods are necessary to confirm HEV infection in suspected cases.

Setsuko Ishida-1

Figure 1

The phylogenetic tree of the HEV sequences detected in clinical samples. HEV strains isolated from a series of 8 patients segregated to a very compact cluster (‚óŹ). This tree is constructed by the neighbour-joining method based on the central region of the ORF2 gene (397 bp). The sequences are designated by the sampling region and sampling date (YYMMDD). For example E-070206 is the sequence obtained from the sample from E region collected in February 6, 2007.


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