Influence of the genetic heterogeneity of the ISDR and PePHD regions of hepatitis C virus on the response to interferon therapy in chronic hepatitis C

Molecular typing of enteroviruses should ideally focus on regions encoding determinants for neutralization. Mapping of monoclonal neutralizing antibodies has shown the VPI protein, in particular its aminoterminal part, encompassing the B-C loop, to be one major antigenic region. We therefore sequenced 570 nucleotides from the 5'-end of the VP1 region of the genome for all 28 echovirus prototypes, and for 61 clinical isolates representing all different echovirus types. An analysis of 133 sequences, including 39 sequences retrieved from GenBank, classified all echoviruses in enterovirus group B confirming results from sequencing within the VP2 region. The nucleotide and amino acid divergence of VP1 sequences of homotypic strains varied from 7.5-23.0% and from 0.0-5.3%, respectively, when compared to their corresponding prototypes, whereas strains belonging to different serotypes these divergences were 22.1-38.9 % and 4.9-16.4 %, respectively. Despite these minimal overlaps, the VP1 sequence was always more similar to that of the homotypic prototype than to that of any heterotypic strain. For 13 out of 14 echovirus types, where multiple isolates were available, the corresponding VP1 sequences diverged more from those of the prototype than from the other homotypic sequences as a reflection of genetic drift. Because there was a complete concordance between the sequences of the region encoding the VP1 aminoterminus and the serotype (P< 0.00001) sequence analysis of this region might complement typing by neutralization, and classify correctly echovirus isolates that may not be typed conveniently by the antisera in hand.