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

• Published in: PloS one Vol. 8; no. 2; p. e56527
• Main Authors: Hardy, Gareth A. D., Sieg, Scott, Rodriguez, Benigno, Anthony, Donald, Asaad, Robert, Jiang, Wei, Mudd, Joseph, Schacker, Timothy, Funderburg, Nicholas T., Pilch-Cooper, Heather A., Debernardo, Robert, Rabin, Ronald L., Lederman, Michael M., Harding, Clifford V.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.02.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Activation; AIDS; Antigens; Antiviral Agents - administration & dosage; Bioassays; Biological activity; Biology; Blood; CD38 antigen; CD4 antigen; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8 antigen; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Chief executive officers; Chronic infection; Correlation; Dendritic cells; Drug therapy; Gene expression; Hepacivirus - drug effects; Hepacivirus - pathogenicity; Hepatitis; Hepatitis C; Hepatitis C - blood; Hepatitis C - drug therapy; HIV; HIV Infections - blood; HIV Infections - immunology; HIV Infections - pathology; HIV-1 - immunology; HIV-1 - pathogenicity; Human immunodeficiency virus; Humans; Immunity, Active; Infections; Infectious diseases; Interferon; Interferon-alpha - administration & dosage; Interferon-alpha - blood; Interferon-alpha - immunology; Leukocytes; Lymph nodes; Lymph Nodes - drug effects; Lymph Nodes - metabolism; Lymphocytes; Lymphocytes T; Medicine; mRNA; Pathogenesis; Pathology; Peripheral blood; Ribavirin; Ribavirin - administration & dosage; Ribonucleic acid; RNA; Viruses; Cleveland Ohio; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056527

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.