title: HIV-1 Nef responsiveness is determined by Env variable regions involved in trimer association and correlates with neutralization sensitivity.
abstract: HIV-1 Nef and the unrelated murine leukemia virus glycoGag similarly enhance the infectivity of HIV-1 virions. We now show that the effects of Nef and glycoGag are similarly determined by variable regions of HIV-1 gp120 that control Env trimer association and neutralization sensitivity. Whereas neutralization-sensitive X4-tropic Env proteins conferred high responsiveness to Nef and glycoGag, particles bearing neutralization-resistant R5-tropic Envs were considerably less affected. The profoundly different Nef/glycoGag responsiveness of a neutralization-resistant and a neutralization-sensitive R5-tropic Env could be switched by exchanging their gp120 V1/V2 regions, which also switches their neutralization sensitivity. Within V1/V2, the same determinants governed Nef/glycoGag responsiveness and neutralization sensitivity, indicating that these phenotypes are mechanistically linked. The V1/V2 and V3 regions, which form an apical trimer-association domain, together determined the Nef and glycoGag responsiveness of an X4-tropic Env. Our results suggest that Nef and glycoGag counteract the inactivation of Env spikes with relatively unstable apical trimer-association domains.
authors.affiliation: Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Usami
authors.forename: Heinrich
authors.initials: H
authors.lastname: Göttlinger
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D014162:Transfection; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D015699:HIV Envelope Protein gp120; D054299:env Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1