Hepatitis B virus (HBV)-specific T-cell responses to recombinant HBV core protein in patients with normal liver function and co-infected with chronic HBV and human immunodeficiency virus 1 (HIV-1)

Virol J. 2013 Jul 12:10:232. doi: 10.1186/1743-422X-10-232.

Abstract

Background: Little is known about HBV-specific T-cell responses in chronic Hepatitis B patients (HBV) that are co-infected with Human immunodeficiency virus type 1 (HIV-1), especially those with normal alanine aminotransferase (ALT) levels.

Methods: Twenty-five patients with chronic HBV (11 hepatitis B e antigen [HBeAg]-positive, 14 HBeAg-negative) were enrolled in a cross-sectional study. A longitudinal study as also conducted in which follow-up was done at 3, 12, and 24 months, after acute HIV-1 infection, in 11 individuals who also had chronic HBV. Peripheral blood mononuclear cells were stimulated with recombinant HBV surface protein (S protein), core protein (C protein) or gag peptide. IFN-γ-secreting T cells were identified by ELISPOT assay.

Results: In the cross-sectional study, co-infected chronic HBV patients had lower C protein-specific T-cell responses compared with mono-infected individuals, though the difference was not significant. In co-infected, chronic HBV patients, the magnitude of C protein-specific T-cell responses was significantly greater in HBeAg-positive subjects compared to HBeAg-negative subjects (p = 0.011). C protein-specific T-cell responses were positively correlated with HBV viral load (rs = 0.40, p = 0.046). However, gag-specific T-cell responses were negatively correlated with HIV viral load (rs = -0.44, p = 0.026) and positively correlated with CD4+ count (rs = 0.46, p = 0.021). The results were different in mono-infected individuals. PBMCs from co-infected HBeAg-positive patients secreted more specific-IFN-γ in cultured supernatants compared with PBMCs from co-infected HBeAg-negative patients (p = 0.019). In the longitudinal study, S protein- and C protein-specific T-cell responses were decreased as the length of follow-up increased (p = 0.034, for S protein; p = 0.105, for C protein). Additionally, the S protein- and C protein-specific T-cell responses were significantly higher in HBeAg-positive patients than in HBeAg-negative patients at 3 and 12 months after HIV-1 infection (all p < 0.05), but not at 24 months. A positive correlation (trend) was found between C protein-specific T-cell responses and HBV viral load at 3 and 12 months after HIV-1 infection.

Conclusions: HBV-specific T-cell responses to recombinant HBV core protein were reduced in chronic HBV patients co-infected with HIV-1. The reduced C protein-specific T cell responses were positively correlated with HBV viral load in co-infected, chronic HBV patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Coinfection / immunology*
  • Cross-Sectional Studies
  • DNA, Viral / blood
  • Enzyme-Linked Immunospot Assay
  • Female
  • HIV Infections / complications
  • HIV Infections / immunology*
  • Hepatitis B Core Antigens / genetics
  • Hepatitis B Core Antigens / immunology*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • T-Lymphocytes / immunology*
  • Viral Load
  • Young Adult

Substances

  • DNA, Viral
  • Hepatitis B Core Antigens
  • Recombinant Proteins
  • Interferon-gamma