Edwin A. Brown

Genetic, antigenic and biological differences between strains of hepatitis A virus.

Recent studies have documented a considerable degree of genetic divergence among wild-type hepatitis A virus (HAV) strains recovered from different geographical locations. Human HAV strains can be grouped into four genotypes (I, II, III and VII) and unique simian strains belong to three additional genotypes (IV, V and VI). Between each of these genotypes, the nucleotide sequence varies at 15-25% of base positions in the P1 region. Despite this, there is good evidence that most, if not all, human strains of HAV are closely related antigenically. In contrast, although simian strains recovered from Old World monkeys are cross-reactive in immunoassays employing polyclonal antibodies, these strains have significant antigenic differences from human HAV strains. Nonetheless, because biological differences in the host range of these strains apparently preclude significant human infection, this is unlikely to pose a problem in controlling HAV infections with active immunization. Inactivated and attenuated vaccines produced from genotype I human strains (HM175 or CR326) are likely to provide protection against all relevant human HAV strains.

Secondary Structure and Protein-binding Activities of the 5′ Nontranslated Region of the Hepatitis C Virus Genome

A model of the secondary structure of the 5′ nontranslated region (5′NTR) of hepatitis C virus (HCV) has been constructed based on the results of a phylogenetic analysis of the nucleotide sequences of the pestiviral and HCV 5′NTRs, and experiments which determined the sites of cleavage of synthetic RNA by single- and double-strand-specific RNases. A uniformly labeled RNA probe representing the 5′ 331 nucleotides (nts) of the 5′NTR (nts 1–331) specifically bound and transferred label to cellular proteins of 39 and 74kDa following UV cross-linking. Competition experiments demonstrated that the domain spanning nts 88–131, which contains a short oligopyrimidine track located at the 5′ end of the putative internal ribosomal entry site (IRES), was required for the binding of these proteins. An unlabeled RNA representing part of the IRES of hepatitis A virus efficiently competed for the binding of these proteins, suggesting that the nontranslated RNAs of these two viruses may share common structures and functions.