University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Date

11-14-2013

Document Type

Article

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

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

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

Comments

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.

Related Resources

Link to Article in PubMed

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.

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.