Influence of specific CD4+ T cells and antibodies on evolution of hypervariable region 1 during acute HCV infection

Journal of Hepatology
Cristiano ScottàAcute Hepatitis C Italian Study Group

Abstract

Several studies suggest that the evolutionary rate of HVR1 sequence in acute HCV hepatitis derives from the action of a continuous immune-driven positive selection. However, these studies have not been performed examining the relationship between HVR1 evolution and the development of specific immunity to autologous HVR1 sequences. We performed a longitudinal analysis of HVR1 sequences and specific antibodies and CD4+ T cells in ten HCV acutely infected patients with different clinical outcomes (recovery versus persistence). We showed that although both recovered and chronically evolving individuals developed IFN-gamma+ T cells specific for Core and NS sequences, HVR1-specific CD4+ T cells were detected only in patients clearing the virus. On the contrary, all patients displayed anti-HVR1 antibodies that recognized sequences exclusively carried by autologous viruses. Measurements of genetic diversity and the number of non-synonymous per synonymous substitutions within HVR1 sequences before and after antibody appearance showed an increase of these parameters only in concomitance with the appearance of anti-HVR1 antibodies. The evidence that anti-HVR1 antibodies favor HVR1 variant selection suggests that viral complexity in chroni...Continue Reading

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Feb 23, 2012·Scientific Reports·David S CampoYury Khudyakov
Nov 18, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael J FullerChristopher M Walker
Aug 6, 2014·Antimicrobial Agents and Chemotherapy·Cassandra B JabaraStanley M Lemon
Jan 28, 2015·World Journal of Hepatology·Babs E VerstrepenGerrit Koopman

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