Program in Gene Function and Expression; Program in Molecular Medicine
Calcium-Binding Proteins; Carrier Proteins; Cell Cycle Proteins; HIV-1; Protein Binding; Protein Interaction Mapping; Protein Structure, Tertiary; gag Gene Products, Human Immunodeficiency Virus
Life Sciences | Medicine and Health Sciences
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.
DOI of Published Version
J Virol. 2008 Feb;82(3):1389-98. Epub 2007 Nov 21. Link to article on publisher's site
Journal of virology
Popov S, Popova E, Inoue M, Gottlinger HG. (2007). Human immunodeficiency virus type 1 Gag engages the Bro1 domain of ALIX/AIP1 through the nucleocapsid. Open Access Publications by UMMS Authors. https://doi.org/10.1128/JVI.01912-07. Retrieved from https://escholarship.umassmed.edu/oapubs/1308