Interferon-α Is the Primary Plasma type-I IFN in HIV-1 Infection and Correlates With Immune Activation and Disease Markers

PLoS One. 2013;8(2):e56527. doi: 10.1371/journal.pone.0056527. Epub 2013 Feb 20.

Abstract

Type-I interferon (IFN-I) has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFNα in HCV-infected subjects to model the effect of IFNα on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012), and IFNα was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001). IFNα was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFNα mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFNα in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003) and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009). In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003). These studies identify IFNα derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antiviral Agents / administration & dosage
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • HIV Infections / blood*
  • HIV Infections / immunology
  • HIV Infections / pathology
  • HIV-1 / immunology
  • HIV-1 / pathogenicity
  • Hepacivirus / drug effects
  • Hepacivirus / pathogenicity
  • Hepatitis C / blood
  • Hepatitis C / drug therapy
  • Humans
  • Immunity, Active*
  • Interferon-alpha / administration & dosage
  • Interferon-alpha / blood
  • Interferon-alpha / immunology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Ribavirin / administration & dosage

Substances

  • Antiviral Agents
  • Interferon-alpha
  • Ribavirin