title: Stoichiometry of envelope glycoprotein trimers in the entry of human immunodeficiency virus type 1.
abstract: The human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs) function as a trimer, mediating virus entry by promoting the fusion of the viral and target cell membranes. HIV-1 Env trimers induce membrane fusion through a pH-independent pathway driven by the interaction between an Env trimer and its cellular receptors, CD4 and CCR5/CXCR4. We studied viruses with mixed heterotrimers of wild-type and dominant-negative Envs to determine the number (T) of Env trimers required for HIV-1 entry. To our surprise, we found that a single Env trimer is capable of supporting HIV-1 entry; i.e., T = 1. A similar approach was applied to investigate the entry stoichiometry of envelope glycoproteins from amphotropic murine leukemia virus (A-MLV), avian sarcoma/leukosis virus type A (ASLV-A), and influenza A virus. When pseudotyped on HIV-1 virions, the A-MLV and ASLV-A Envs also exhibit a T = 1 entry stoichiometry. In contrast, eight to nine influenza A virus hemagglutinin trimers function cooperatively to achieve membrane fusion and virus entry, using a pH-dependent pathway. The different entry requirements for cooperativity among Env trimers for retroviruses and influenza A virus may influence viral strategies for replication and evasion of the immune system.
authors.affiliation: Dana-Farber Cancer Institute, Department of Cancer Immunology and AIDS, 44 Binney Street, JFB 824, Boston, MA 02115, USA. xinzhen_yang@dfci.harvard.edu
authors.forename: Xinzhen
authors.initials: X
authors.lastname: Yang
authors.forename: Svetla
authors.initials: S
authors.lastname: Kurteva
authors.forename: Xinping
authors.initials: X
authors.lastname: Ren
authors.forename: Sandra
authors.initials: S
authors.lastname: Lee
authors.forename: Joseph
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D001358:Avian Sarcoma Viruses / Q000502:physiology; D002460:Cell Line; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009980:Influenza A virus / Q000502:physiology; D009052:Leukemia Virus, Murine / Q000502:physiology; D008561:Membrane Fusion; D009154:Mutation; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
chemical_list: D014759:Viral Envelope Proteins