Analysis of the core region of HCV genome isolated from patients with chronic hepatitis C during intervals of normal ALT concentration

Abstract

We determined the core region nucleotide and amino acid sequences in specimens from two patients with chronic hepatitis C during intervals of normal and elevated alanine aminotransferase (ALT) concentrations. When the ALT concentrations remained normal, the serum HCR-RNA concentration exceeded that before therapy and most of the clones that could be sequenced had a deletion or an amber mutation. The clones isolated from a HLA B44-positive patient had a mutation at amino acid 91. These results suggest that expression of the wild-type HCV core region genome may be associated with liver cell damage.

Magnitude of activity in chronic hepatitis C is influenced by apoptosis of T cells responsible for hepatitis C virus

“…This result is thought to due to the fact that most of the epitopes from the JCC‐1 antigen are different to the epitopes from the HCV strains infecting each patient. A low SI in the proliferation assay shown in other reports 21 and the present results may also be attributed to the multiantigenic epitopes 8,9 and multispecies of HCV strains; 10,11 that is, differences in amino acid sequences may exist between antigens found in vivo in patients with CHC and the recombinant HCV‐related antigens used in vitro . It is, therefore, natural that T cell proliferation to JCC‐1 antigen did not correlate with the degree of apoptosis in freshly obtained T cells, but it is somewhat strange that apoptosis in freshly obtained T cells could not be related to sALT, because one can propose that a high value of sALT reflects the fact that T cells are effectively stimulated in vivo with optimal epitopes, leading to proliferation but not to apoptosis.…”

“… 13 In patients with CHC, many analogues of immunogenic (optimal) epitopes are believed to exist. 8–11 Apoptosis of T cells in patients with CHC can, therefore, be induced by different analogues. However, some analogues cannot deliver a full stimulatory signal, thus inducing anergy, 14,15 or acting as an antagonist for TcR.…”

“… 8,9 Patients may also be simultaneously infected by multispecies of HCV strains. 10,11 Multispecies of epitopes derived from HCV, associating with a T cell antigen receptor (TcR), therefore, must exist simultaneously in individuals with CHC. We supposed that peripheral T cells responsible for HCV‐related antigens can also undergo apoptosis in patients with CHC where many analogues of immunogenic (optimal) epitopes exist.…”