UMMS Affiliation

Program in Gene Function and Expression

Date

3-7-2008

Document Type

Article

Subjects

Amino Acid Motifs; Cell Line; HIV-1; Humans; Protein Binding; Protein Interaction Mapping; Ubiquitin; Ubiquitin-Protein Ligases; gag Gene Products, Human Immunodeficiency Virus

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and LYPx(n)L late assembly (L) domains. In contrast, less-complex retroviruses often use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically active HECT domain and was specific, since other Nedd4 family proteins showed little activity and an unrelated retrovirus was not rescued. The residual C2 domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the association of Nedd4-2s with Gag, as reflected by its incorporation into virus-like particles. Interestingly, the incorporation of Nedd4-2s also depended on its active site, indicating that the ability to form a thioester with ubiquitin was required. These data suggest a novel mechanism by which HIV-1 Gag can connect to cellular budding machinery.

Rights and Permissions

Citation: J Virol. 2008 May;82(10):4898-907. Epub 2008 Mar 5. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.02675-07

Related Resources

Link to Article in PubMed

Journal Title

Journal of virology

PubMed ID

18321969

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