Evidence for hepatitis E virus quasispecies.

The genetic diversity of hepatitis E virus (HEV) has been extensively analysed during the last decade. Most sporadic and epidemic HEV strains are distributed into genotypes or groups. Nevertheless, few studies have looked at the polymorphism of HEV strains isolated from a given outbreak. A serum bank collected in Tanefdour, Algeria, during an acute hepatitis epidemic (1986-1987), retrospectively confirmed as hepatitis E, was analysed. Of the 69 serum samples collected within an 8-week period, 23 were positive for both partial ORF1 (replicase gene) and ORF2 (capsid gene) sequences. Inter- and intra-patient diversities were assessed by RFLP, and by sequencing a 448 bp sequence corresponding to ORF2. RFLP analysis distinguished three profiles: A (18/23), B (3/23) and C (2/23). Most isolates (18/23) shared 99.7-100 % sequence identity and the remainder showed 1-1.3 % divergence. HEV intra-patient diversity was studied using 12 isolates (seven displaying the major RFLP profile and five displaying minor RFLP profiles). For 9 of 12 isolates, additional intra-patient heterogeneity was revealed by RFLP analysis of 100 clones from each isolate and sequence diversity ranging from 0.11 to 3.4 %. These data strongly support the quasispecies organization of HEV during epidemics and could explain the adaptable behaviour of the virus in the host-pathogen interrelations.