title: Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.
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.
authors: Department of Pathology, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio, USA.
authors: Gareth A D
authors: GA
authors: Hardy
authors: Scott
authors: S
authors: Sieg
authors: Benigno
authors: B
authors: Rodriguez
authors: Donald
authors: D
authors: Anthony
authors: Robert
authors: R
authors: Asaad
authors: Wei
authors: W
authors: Jiang
authors: Joseph
authors: J
authors: Mudd
authors: Timothy
authors: T
authors: Schacker
authors: Nicholas T
authors: NT
authors: Funderburg
authors: Heather A
authors: HA
authors: Pilch-Cooper
authors: Robert
authors: R
authors: Debernardo
authors: Ronald L
authors: RL
authors: Rabin
authors: Michael M
authors: MM
authors: Lederman
authors: Clifford V
authors: CV
authors: Harding
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D015658:HIV Infections / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D016174:Hepacivirus / Q000187:drug effects / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy; D006801:Humans; D007110:Immunity, Active; D016898:Interferon-alpha / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D012254:Ribavirin / Q000008:administration & dosage
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin