title: Inhibition of HIV-1 infectivity through an innate mechanism involving naturally occurring IgM anti-leukocyte autoantibodies.
abstract: In prior studies, we show that naturally occurring IgM anti-leukocyte autoantibodies (IgM-ALA) bind to CD3, CD4, CCR5, and CXCR4 receptors. These observations prompted us to determine whether IgM-ALA have a role in inhibiting HIV-1 infectivity by inhibiting viral entry into cells. We show that purified IgM, but not IgG, from individual sera of both normal and HIV-1 infected individuals is highly inhibitory (>95%) to HIV-1 viral infectivity both in vitro using PHA plus IL-2 activated PBL and in vivo using the human PBL-SCID mouse. Inhibition was observed with physiological doses of purified serum IgM and even after IgM was added 3 days postinfection in the in vitro assays. Absorbing purified serum IgM either with leukocytes or immobilized recombinant CD4 significantly decreased (>80%) the inhibitory effect on HIV-1 infectivity. IgM inhibited by >90% syncytia formation with the X4-IIIB infected SupT-1 cells indicating therefore that IgM inhibits viral attachment to core-receptors. IgM mediated anti-HIV-1 activity was highly specific as only certain IgM-ALA, obtained from human B cell clones inhibited HIV-1. IgM from certain HIV-1 infected individuals were not inhibitory to some R5-HIV-1 viral strains indicating that certain HIV-IgM may lack Abs reactive to strain specific coreceptor epitopes. These data indicate that an innate immune mechanism which is present from birth i.e., IgM-ALA, has a role in inhibiting HIV-1 viral entry into cells. Validation of this data with other in vivo models will be needed to determine whether in vivo administration or enhancement of IgM-ALA, e.g., through a vaccine, could prolong the asymptomatic state in HIV-1 infected individuals.
authors.affiliation: Division of Nephrology, Center for Immunity Inflammation and Regenerative Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA. pil@virginia.edu
authors.forename: Peter I
authors.initials: PI
authors.lastname: Lobo
authors.forename: Kailo H
authors.initials: KH
authors.lastname: Schlegel
authors.forename: Wen
authors.initials: W
authors.lastname: Yuan
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Townsend
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: White
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D015726:Giant Cells / Q000187:drug effects / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D007676:Kidney Failure, Chronic / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000276:immunology; D053586:Virus Internalization / Q000187:drug effects*
chemical_list: D001323:Autoantibodies; D015704:CD4 Antigens; D015483:HIV Antibodies; D007075:Immunoglobulin M; D019718:Receptors, CXCR4