title: Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections.
abstract: Characterization of the immune responses induced in the initial stages of human immunodeficiency virus type 1 (HIV-1) infection is of critical importance for an understanding of early viral pathogenesis and prophylactic vaccine design. Here, we used sequential plasma samples collected during the eclipse and exponential viral expansion phases from subjects acquiring HIV-1 (or, for comparison, hepatitis B virus [HBV]or hepatitis C virus [HCV]) to determine the nature and kinetics of the earliest systemic elevations in cytokine and chemokine levels in each infection. Plasma viremia was quantitated over time, and levels of 30 cytokines and chemokines were measured using Luminex-based multiplex assays and enzyme-linked immunosorbent assays. The increase in plasma viremia in acute HIV-1 infection was found to be associated with elevations in plasma levels of multiple cytokines and chemokines, including rapid and transient elevations in alpha interferon (IFN-alpha) and interleukin-15 (IL-15) levels; a large increase in inducible protein 10 (IP-10) levels; rapid and more-sustained increases in tumor necrosis factor alpha and monocyte chemotactic protein 1 levels; more slowly initiated elevations in levels of additional proinflammatory factors including IL-6, IL-8, IL-18, and IFN-gamma; and a late-peaking increase in levels of the immunoregulatory cytokine IL-10. Notably, there was comparatively little perturbation in plasma cytokine levels during the same phase of HBV infection and a delayed response of more intermediate magnitude in acute HCV infection, indicating that the rapid activation of a striking systemic cytokine cascade is not a prerequisite for viral clearance (which occurs in a majority of HBV-infected individuals). The intense early cytokine storm in acute HIV-1 infection may have immunopathological consequences, promoting immune activation, viral replication, and CD4(+) T-cell loss.
authors.affiliation: The Jenner Institute, University of Oxford, Compton, Berkshire RG20 7NN, United Kingdom.
authors.forename: Andrea R
authors.initials: AR
authors.lastname: Stacey
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Norris
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Haygreen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Taylor
authors.forename: John
authors.initials: J
authors.lastname: Heitman
authors.forename: Mila
authors.initials: M
authors.lastname: Lebedeva
authors.forename: Allan
authors.initials: A
authors.lastname: DeCamp
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Li
authors.forename: Douglas
authors.initials: D
authors.lastname: Grove
authors.forename: Steven G
authors.initials: SG
authors.lastname: Self
authors.forename: Persephone
authors.initials: P
authors.lastname: Borrow
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006509:Hepatitis B / Q000276:immunology / Q000821:virology; D006515:Hepatitis B virus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D006801:Humans; D008137:Longitudinal Studies; D010949:Plasma / Q000737:chemistry / Q000821:virology; D014766:Viremia
chemical_list: D016207:Cytokines