Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection

Chris L. Ayers, Mihail Firan, Vinodh Pillai, William M. Lee, Nitin J. Karandikar

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Hepatitis C virus (HCV) has a propensity to establish chronic infection that is characterized by attenuated virus-specific T-cell responses. Mechanisms leading to T-cell attenuation are poorly understood and likely involve dysfunctional interactions between antigen-presenting cells (APC) and effector/regulatory T-cells. Reports on dendritic cells (DC) have described only minor dysfunction during HCV infection. However, there is a paucity of reports regarding B-cell function, despite clear associations with B-cell-related secondary sequelae. In this study we evaluated the state of B-cells during chronic HCV infection, and observed a diminished ability to respond to mitogenic stimuli, correlating with increased apoptosis. This was in contrast to their ex vivo phenotype, which indicated ongoing chronic activation in vivo. There was a high association of HCV-positive strand RNA with B-cells in a subset of HCV patients. Interestingly, ex-vivo-derived HCV RNA-positive B-cells induced significantly greater proliferation in allogeneic T-cells than in HCV-negative B-cells, correlating with an increased generation of CD4+CD25 +FOXP3+ regulatory T-cells (Tregs). In-vitro exposure of healthy peripheral blood mononuclear cells (PBMC) to HCV resulted in robust activation of resting B-cells. These HCV-exposed B-cells also showed an enhanced ability to generate Tregs. Our results provide strong evidence for a novel and paradoxical link between HCV-induced enhanced APC function and the generation of Tregs.

Original languageEnglish (US)
Pages (from-to)119-129
Number of pages11
JournalViral Immunology
Issue number2
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Immunology
  • Molecular Medicine
  • Virology


Dive into the research topics of 'Viral interactions with B-cells contribute to increased regulatory T-cells during chronic HCV infection'. Together they form a unique fingerprint.

Cite this