University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Publication Date

11-14-2013

Document Type

Article

Subjects

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

Disciplines

Genetics and Genomics | Immunology and Infectious Disease | Immunology of Infectious Disease | Virology

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.

Rights and Permissions

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI of Published Version

10.1016/j.celrep.2013.09.028

Source

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

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Cell reports

PubMed ID

24209751

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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