Program in Gene Function and Expression; Program in Molecular Medicine
Medical Subject Headings
Alleles; Amino Acid Sequence; HEK293 Cells; HIV Envelope Protein gp120; HIV Infections; HIV-1; Humans; Molecular Sequence Data; Transfection; env Gene Products, Human Immunodeficiency Virus; nef Gene Products, Human Immunodeficiency Virus
Genetics and Genomics | Immunology and Infectious Disease | Immunology of Infectious Disease | Virology
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.
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Citation: Cell Rep. 2013 Nov 14;5(3):802-12. doi: 10.1016/j.celrep.2013.09.028. Epub 2013 Oct 24. Link to article on publisher's site
Usami, Yoshiko and Gottlinger, Heinrich G., "HIV-1 Nef responsiveness is determined by Env variable regions involved in trimer association and correlates with neutralization sensitivity" (2013). University of Massachusetts Medical School Faculty Publications. 806.
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