title: Role of virion-associated glycosylphosphatidylinositol-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1.
abstract: This study investigates whether cell-derived glycosylphosphatidylinositol-linked complement control proteins CD55 and CD59 can be incorporated into HIV-1 virions and contribute to complement resistance. Virus was prepared by transfection of cell lines with pNL4-3, and primary isolates of HIV-1 were derived from patients' PBMCs. Virus was tested for sensitivity to complement-mediated virolysis in the presence of anti-gp160 antibody. Viral preparations from JY33 cells, which lack CD55 and CD59, were highly sensitive to complement. HIV-1 preparations from H9 and U937 cells, which express low levels of CD55 and CD59, had intermediate to high sensitivity while other cell line-derived viruses and primary isolates of HIV-1 were resistant to complement-mediated virolysis. Although the primary isolates were not lysed, they activated complement as measured by binding to a complement receptor positive cell line. While the primary isolates were resistant to lysis in the presence of HIV-specific antibody, antibody to CD59 induced lysis. Likewise, antibody to CD55 and CD59 induced lysis of cell line-derived virus. Western blot analysis of purified virus showed bands corresponding to CD55 and CD59. Phosphatidylinositol-specific phospholipase C treatment of either cell line-derived or primary isolates of HIV-1 increased sensitivity to complement while incubation of sensitive virus with purified CD55 and CD59 increased resistance to complement. These results show that CD55 and CD59 are incorporated into HIV-1 particles and function to protect virions from complement-mediated destruction, and they are the first report of host cell proteins functioning in protection of HIV-1 from immune effector mechanisms.
authors.affiliation: Department of Immunology/Microbiology, Rush University, Chicago, Illinois 60612, USA.
authors.forename: M
authors.initials: M
authors.lastname: Saifuddin
authors.forename: C J
authors.initials: CJ
authors.lastname: Parker
authors.forename: M E
authors.initials: ME
authors.lastname: Peeples
authors.forename: M K
authors.initials: MK
authors.lastname: Gorny
authors.forename: S
authors.initials: S
authors.lastname: Zolla-Pazner
authors.forename: M
authors.initials: M
authors.lastname: Ghassemi
authors.forename: I A
authors.initials: IA
authors.lastname: Rooney
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: G T
authors.initials: GT
authors.lastname: Spear
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D018958:CD55 Antigens; D018957:CD59 Antigens; D002460:Cell Line; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D008562:Membrane Glycoproteins / Q000378:metabolism*; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D018958:CD55 Antigens; D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; D008562:Membrane Glycoproteins; D003165:Complement System Proteins; D010727:Phosphoric Diester Hydrolases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase