T lymphocytes in primary cultures. Exposure of lymphoid
cells to 2 of 3 HCV inocula caused a decrease in the
frequency of CD4+ T cells compared to virus-untreated
cultures with a relative increase in CD8+ T cells. This
relative CD8+ T cell enrichment was a result of a significant
reduction in CD4+ T cell proliferation compared to
the cultures exposed to normal healthy plasma. On this
note, the effect appeared to correlate with HCV cell uptake,
since the shift in the CD4+ to CD8+ ratio was highest
in the cultures in which virus exposure lead to
quantifiable levels of HCV RNA positive strands and, in
the case of CHC-1, negative strands in test cells
(Table 1). This was consistent with the observation that
in cultures exposed to CHC-1 inoculum, which induced
the highest levels of HCV RNA positive strand and detectable
HCV RNA negative strand, the inhibition in
CD4+ T cell proliferation appeared earlier, i.e., 4 d.p.i.
In the cells exposed to CHC-2 inoculum, T cell proliferative
and phenotypic changes were seen in the absence
of detectable HCV replicative intermediate and
after 10-fold lower multiplicity of infection compared
to cells exposed to CHC-1. In the case of CHC-3, while
the plasma viral load was higher than CHC-2 and comparable
to CHC-1, there did not appear to be much
virus uptake by cells, as indicated by undetectable
HCV RNA by our high sensitivity assays. This may
suggest that the amount of virus taken by cells exposed
to CHC-3 was minuscule. HCV genotype may also play
a role in the anti-proliferative effects observed, as
CHC-1 carried an HCV genotype 1a/1b mix, CHC-2
genotype 3a, and CHC-3 genotype 2b. It is of note that
there was no impact of TLP treatment on the change
in the CD4+ and CD8+ T cell frequency, which suggests
that exposure to HCV and uptake of the virus by