Viral Escape and the Failure of Cellular Immune Responses
This Week in SCIENCE
September 22 2000, 289 (5487)

Farci et al. (Reports, 14 April, p. 339), studying the evolution of
sequences in the envelope genes of the hepatitis C virus (HCV), found that
HCV evolved rapidly and showed much more genetic diversity in patients who
developed the chronic form of the disease than it did in patients who
ultimately cleared the virus. The data, they concluded, "indicate that the
evolutionary dynamics of the HCV quasispecies during the acute phase of
hepatitis C predict whether the infection will resolve or become chronic."
Klenerman et al., while acknowledging that reduced viral diversity indeed
probably constitutes "a feature of more successful immune responses," argue
that "an appropriate balance between cellular and humoral immune responses"
--i.e., between the early response by CD8+ cytotoxic T lymphocytes (CTLs)
and subsequent pressure from neutralizing antibodies--is another important,
and often overlooked, element of immune system success against this virus.
Farci et al., in their response, agree that "the cellular and humoral
components of the immune system together induce definitive viral
clearance," in marked contrast to "the reductionist theories of either CTL
dominance or antibody dominance that have hitherto prevailed in studies of
sterilizing immunity."