title: CD4-independent binding of SIV gp120 to rhesus CCR5.
abstract: CCR5 and CD4 are coreceptors for immunodeficiency virus entry into target cells. The gp120 envelope glycoprotein from human immunodeficiency virus strain HIV-1(YU2) bound human CCR5 (CCR5hu) or rhesus macaque CCR5 (CCR5rh) only in the presence of CD4. The gp120 from simian immunodeficiency virus strain SIVmac239 bound CCR5rh without CD4, but CCR5hu remained CD4-dependent. The CD4-independent binding of SIVmac239 gp120 depended on a single amino acid, Asp13, in the CCR5rh amino-terminus. Thus, CCR5-binding moieties on the immunodeficiency virus envelope glycoprotein can be generated by interaction with CD4 or by direct interaction with the CCR5 amino-terminus. These results may have implications for the evolution of receptor use among lentiviruses as well as utility in the development of effective intervention.
authors.affiliation: Perlmutter Laboratory, Children's Hospital, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Martin
authors.forename: R
authors.initials: R
authors.lastname: Wyatt
authors.forename: M
authors.initials: M
authors.lastname: Farzan
authors.forename: H
authors.initials: H
authors.lastname: Choe
authors.forename: L
authors.initials: L
authors.lastname: Marcon
authors.forename: E
authors.initials: E
authors.lastname: Desjardins
authors.forename: J
authors.initials: J
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
authors.forename: C
authors.initials: C
authors.lastname: Gerard
authors.forename: N P
authors.initials: NP
authors.lastname: Gerard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000502:physiology*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015498:HIV-2 / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D008264:Macrophages / Q000821:virology; D008562:Membrane Glycoproteins; D009154:Mutation; D019713:Receptors, CCR5 / Q000737:chemistry / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D014162:Transfection; D014759:Viral Envelope Proteins
chemical_list: D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D008562:Membrane Glycoproteins; D019713:Receptors, CCR5; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus