UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine

Publication Date

11-23-2007

Document Type

Article

Subjects

Calcium-Binding Proteins; Carrier Proteins; Cell Cycle Proteins; HIV-1; Protein Binding; Protein Interaction Mapping; Protein Structure, Tertiary; gag Gene Products, Human Immunodeficiency Virus

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Human immunodeficiency virus type 1 (HIV-1) and other retroviruses harbor short peptide motifs in Gag that promote the release of infectious virions. These motifs, known as late assembly (L) domains, recruit a cellular budding machinery that is required for the formation of multivesicular bodies (MVBs). The primary L domain of HIV-1 maps to a PTAP motif in the p6 region of Gag and engages the MVB pathway by binding to Tsg101. Additionally, HIV-1 p6 harbors an auxiliary L domain that binds to the V domain of ALIX, another component of the MVB pathway. We now show that ALIX also binds to the nucleocapsid (NC) domain of HIV-1 Gag and that ALIX and its isolated Bro1 domain can be specifically packaged into viral particles via NC. The interaction with ALIX depended on the zinc fingers of NC, which mediate the specific packaging of genomic viral RNA, but was not disrupted by nuclease treatment. We also observed that HIV-1 zinc finger mutants were defective for particle production and exhibited a similar defect in Gag processing as a PTAP deletion mutant. The effects of the zinc finger and PTAP mutations were not additive, suggesting a functional relationship between NC and p6. However, in contrast to the PTAP deletion mutant, the double mutants could not be rescued by overexpressing ALIX, further supporting the notion that NC plays a role in virus release.

Rights and Permissions

Citation: J Virol. 2008 Feb;82(3):1389-98. Epub 2007 Nov 21. Link to article on publisher's site

DOI of Published Version

10.1128/JVI.01912-07

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

18032513

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