Structure and Function of the Hepatitis E Virus Capsid Related to Hepatitis E Pathogenesis

There are five different types of viral hepatitis (A, B, C, D, and E) in the world, each of which caused by a different virus. Although they all cause the disease in human, the five viruses are unrelated and are from different virus families with totally different genome structures and distinct replication mechanisms (Fauquet et al., 2005; Hochman & Balistreri, 1999; Kumar et al., 2010). Hepatitis E is an acute viral hepatitis caused by hepatitis E virus (HEV) which is transmitted primarily through a fecal-oral route (Knipe et al., 2007). Pregnancy is one of the risk factors for severe HEV infection with high mortality rate. Numerous epidemic and sporadic cases have occurred in developing countries of Asia, the Middle East, and North Africa, where sanitary conditions are not well-maintained (Okamoto, 2007; Panda et al., 2007; Vasickova et al., 2007). Recent epidemiological studies show that significant prevalence of HEV and anti-HEV antibody is found in humans and several kinds of wild and domestic animals worldwide, including industrialized countries (Meng, 2010). Hepatitis E virus, discovered in 1983 by immune electron microscopy (Balayan et al., 1983) and first cloned in 1990 (Reyes et al., 1990), is the sole member of the genus Hepevirus within the family Hepeviridae. Based on genome sequences, five major genotypes have been identified. The circulation of genotypes 1 and 2 viruses is maintained among only humans, while those of genotypes 3 and 4 are found in human as well as animals. The viruses of genotype 5 are of avian origin, thought to be noninfectious to humans. Although four of the five genotypes infect human ,only one HEV serotype has been found in human (Okamoto, 2007). HEV is composed of a protein capsid made of a single protein and a positive-sense RNA genome of 7.2 to 7.8 kb in size. Like the hepatitis A virus (HAV), HEV does not have a viral envelope, different from the hepatitis B, C, D virus, all of which contain membrane envelopes outside their capsid. The genomic RNA of HEV is capped, polyadenylated, containing three open reading frames (ORFs). ORF1, mapped at the 5’ terminus of the genome, has about 5124 bases and encodes several viral nonstructural proteins (e.g. methyltransferase, protease, helicase and RNA-dependent RNA polymerase). ORF2 contains 1980 bases at the 3’ end of the genome and encodes the viral capsid protein (CP).