No abstract

Hepatitis E virus (HEV) is a causative agent of enterically transmitted non-A, non-B hepatitis. Hepatitis E occurs not only in sporadic forms but also in epidemic outbreaks in the developing world. We have revealed the nucleotide and predicted amino acid sequences of full cDNA of HEV isolated from sporadic hepatitis E of Myanmar. The genome is 7194 nucleotides long, followed by a poly(A) tail, and has three open reading frames. The nonstructural gene is located in the 5' terminus, while the structural gene is situated in the 3' terminus. Our HEV strain has 98.5% nucleic acid identity with the HEV strain cloned by workers at Genelabs Incorporated from Myanmar. The difference is point nucleotide substitutions. There is a high degree of nucleotide relatedness among HEVs isolated from the same geographical location.

An epidemic outbreak of hepatitis E occurred in an army recruit camp of Yangon, Myanmar, in October 1989. One hundred and eleven patients among 600 residents were hospitalized. As high as 83.7% of these patients were positive for the acute phase antibody against hepatitis E virus by an enzyme‐linked immunosorbent assay developed in our laboratory. Also, 30.6% of 49 symptom‐free residents examined were positive for the antibody. We prepared a stool extract from six patients and inoculated it into 10 rhesus monkeys for a series of three subpassages. All of them developed acute biochemical hepatitis along with an elevation of antibody levels. A rechallenge with viruses of the present outbreak failed to provoke hepatitis in two monkeys that had previously recovered from acute hepatitis caused by an isolate of sporadic hepatitis E of the same area. Similarly, the rechallenge of the sporadic strain did not induce hepatitis in two monkeys that had been previously infected with the epidemic virus. These data suggested that the subjects would obtain neutralizing antibodies against the hepatitis E virus once infected, and many adult inhabitants of the endemic area had no protective antibodies and were still susceptible to hepatitis E infection.

Hepatitis E viruses (HEVs) were isolated during epidemics, one from Myanmar (formerly called Burma) and one from China and were partially sequenced. Another HEV Myanmar strain from sporadic hepatitis was previously sequenced by us. A cDNA seq uence comparison was performed among them in the 3'-terminal region, approximately 750-base long. This region contained at least two immunological epitopes and was considered to correspond to the structural protein. The nucleotide sequence identity was 97.2% between the two Myanmar strains and 93.3 and 92.5% between the two Myanmar and the China strain. The deduced amino acid sequence identity ranged from 98.4 to 100.0% among the three strains. Thus this segment was well conserved on the amino acid level among the different strains isolated from these two Asian countries, although the China strain diverged more from the Myanmar strains on the nucleotide sequence level. This data may provide important information for the development of a vaccine and for identification of the virological link between different geographical locations.Hepatitis E is prevalent in many developing countries, predominantly in tropical and subtropical areas. In these countries it provokes epidemic outbreaks frequently involving more than several thousand patients (8) and sporadic hepatitis in the periods between epidemics. Hepatitis E may not be endemic to the industrialized countries; however, it does occur as "imported hepatitis" via immigrants, tourists or workers (6, 10). A vaccination must be developed to eradicate hepatitis E from the world.The HEV has a single-stranded, plus-sense RNA genome, approximately 8.6-kilobase long (14). Viral full-length cDNA was sequenced by Reyes and his colleagues (17), and by us as well (1). Their and our viruses originated from hepatitis E from Yangon (formerly called Rangoon) of Myanmar. In other cases, we partially sequenced strains isolated from epidemic hepatitis E in Yangon (Uchida et al, submitted for publication) and in China (3).