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

Cristiano Scottà, Anna Rosa Garbuglia, Lionello Ruggeri, Enea Spada, Luca Laurenti, Maria Paola Perrone, Gabriella Girelli, Alfonso Mele, Maria Rosaria Capobianchi, Antonella Folgori, Alfredo Nicosia, Paola Del Porto, Enza Piccolella

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aims: 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. Methods: 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). Results: We showed that although both recovered and chronically evolving individuals developed IFN-γ+ 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. Conclusions: The evidence that anti-HVR1 antibodies favor HVR1 variant selection suggests that viral complexity in chronically infected patients could represent a virus adaptive strategy to escape the continuous selective process mediated by anti-HVR1 antibodies.

Original languageEnglish
Pages (from-to)216-228
Number of pages13
JournalJournal of Hepatology
Volume48
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • Cellular immune response
  • Genetic diversity
  • HCV acute infection
  • Humoral immune response
  • Hypervariable region 1

ASJC Scopus subject areas

  • Gastroenterology

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