title: Glycosylphosphatidylinositol Anchor Deficiency Attenuates the Production of Infectious HIV-1 and Renders Virions Sensitive to Complement Attack.
abstract: Human immunodeficiency virus type 1 (HIV-1) escapes complement-mediated lysis (CML) by incorporating host regulators of complement activation (RCA) into its envelope. CD59, a key member of RCA, is incorporated into HIV-1 virions at levels that protect against CML. Since CD59 is a glycosylphosphatidylinositol-anchored protein (GPI-AP), we used GPI anchor-deficient Jurkat cells (Jurkat-7) that express intracellular CD59, but not surface CD59, to study the molecular mechanisms underlying CD59 incorporation into HIV-1 virions and the role of host proteins in virus replication. Compared to Jurkat cells, Jurkat-7 cells were less supportive to HIV-1 replication and more sensitive to CML. Jurkat-7 cells exhibited similar capacities of HIV-1 binding and entry to Jurkat cells, but were less supportive to viral RNA and DNA biosynthesis as infected Jurkat-7 cells produced reduced amounts of HIV-1 RNA and DNA. HIV-1 virions produced from Jurkat-7 cells were CD59 negative, suggesting that viral particles acquire CD59, and probably other host proteins, from the cell membrane rather than intracellular compartments. As a result, CD59-negative virions were sensitive to CML. Strikingly, these virions exhibited reduced activity of virus binding and were less infectious, implicating that GPI-APs may be also important in ensuring the integrity of HIV-1 particles. Transient expression of the PIG-A gene restored CD59 expression on the surface of Jurkat-7 cells. After HIV-1 infection, the restored CD59 was colocalized with viral envelope glycoprotein gp120/gp41 within lipid rafts, which is identical to that on infected Jurkat cells. Thus, HIV-1 virions acquire RCA from the cell surface, likely lipid rafts, to escape CML and ensure viral infectivity.
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Tohti
authors.initials: T
authors.lastname: Amet
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Jie
authors.initials: J
authors.lastname: Lan
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Nicole
authors.initials: N
authors.lastname: Shepherd
authors.affiliation: 2 Wenzhou Institute of Biomaterials and Engineering , Wenzhou, China .
authors.forename: Kai
authors.initials: K
authors.lastname: Yang
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Byrd
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.|3 Department of Pathophysiology, Medical College of Jinan University , Guangzhou, China .
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: 1 Department of Microbiology and Immunology, Indiana Center for AIDS Research, Indiana University School of Medicine , Indianapolis, Indiana.|2 Wenzhou Institute of Biomaterials and Engineering , Wenzhou, China .|4 Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine , Indianapolis, Indiana.
authors.forename: Qigui
authors.initials: Q
authors.lastname: Yu
mesh_terms: D018957:CD59 Antigens / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology*; D017261:Glycosylphosphatidylinositols / Q000172:deficiency*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D019169:Jurkat Cells; D014771:Virion / Q000276:immunology* / Q000502:physiology*; D019065:Virus Assembly
chemical_list: D018957:CD59 Antigens; D017261:Glycosylphosphatidylinositols; C051590:CD59 protein, human; D003165:Complement System Proteins
keywords: GPI-AP; HIV-1; antibody; complement; virus binding; virus replication