HCV core/gC1qR interaction arrests T cell cycle progression through stabilization of the cell cycle inhibitor p27Kip1.
Hepatitis C virus (HCV) is efficient in the establishment of persistent infection. We have previously shown that HCV core protein inhibits T cell proliferation through its interaction with the complement receptor, gC1qR. Here we show that HCV core-induced inhibition of T cell proliferation involves a G(0)/G(1) cell cycle arrest, which is reversible upon addition of anti-gC1qR antibody. Correspondingly, the expression of cyclin-dependent kinases (Cdk) 2/4 and cyclin E/D, as well as subsequent phosphorylation of retinoblastoma (pRb), is reduced in core-treated T cells in response to mitogenic stimulation. Remarkably, degradation of p27(Kip1), a negative regulator of both Cdk4/cyclin D and Cdk2/cyclin E complexes, is significantly diminished in T cells treated with HCV core upon mitogenic stimulation. These data indicate that the stability of p27(Kip1) by HCV core is associated with blocking activated T cells for the G(1) to S phase transition and inhibiting T cell proliferation.
D002352:Carrier Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016193:G1 Phase / Q000502:physiology; D016174:Hepacivirus / Q000472:pathogenicity*; D006801:Humans; D018960:Hyaluronan Receptors; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement / Q000378:metabolism*; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D016196:S Phase / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014758:Viral Core Proteins / Q000378:metabolism*
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D011951:Receptors, Complement; D025521:Tumor Suppressor Proteins; D014758:Viral Core Proteins; C032402:complement 1q receptor; C069130:nucleocapsid protein, Hepatitis C virus; D050760:Cyclin-Dependent Kinase Inhibitor p27