Hepatitis C virus (HCV) has been shown to actively replicate in cells of
the immune system, altering both their function and cytokine expression.
Naked nucleocapsids have been reported in the serum of infected
patients. We investigated interference of recombinant non-enveloped
capsid-like particles with signaling pathways in T cells. HCV
non-enveloped particles (HCVne) internalization was verified in Jurkat
and Hut 78 T cells, as well as primary human peripheral blood and
intrahepatic mononuclear cells. HCVne uptake leads to activation of the
MAPKs-p38 signaling pathway. Using specific phosphoantibodies, signaling
pathways inhibitors, and chemical agents, it was demonstrated that p38
activation in T cells correlated with IL-2 transcriptional activation
and was accompanied by a parallel increase of IL-2 cytokine secretion.
c-fos and egr-1, two transcription factors, essential for IL-2 promoter
activity, were also found to be elevated. We propose that HCVne uptake
by T lymphocytes results in increased MAPKs-p38 activity and IL-2
expression, thus altering the host immune response
