Gag regulates association of human immunodeficiency virus type 1 envelope with detergent-resistant membranes

Program in Molecular Medicine, Center for AIDS Research, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Journal of Virology (Impact Factor: 4.65). 07/2006; 80(11):5292-300. DOI: 10.1128/JVI.01469-05
Source: PubMed

ABSTRACT Assembly of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein on budding virus particles is important for efficient infection of target cells. In infected cells, lipid rafts have been proposed to form platforms for virus assembly and budding. Gag precursors partly associate with detergent-resistant membranes (DRMs) that are believed to represent lipid rafts. The cytoplasmic domain of the envelope gp41 usually carries palmitate groups that were also reported to confer DRM association. Gag precursors confer budding and carry envelope glycoproteins onto virions via specific Gag-envelope interactions. Thus, specific mutations in both the matrix domain of the Gag precursor and gp41 cytoplasmic domain abrogate envelope incorporation onto virions. Here, we show that HIV-1 envelope association with DRMs is directly influenced by its interaction with Gag. Thus, in the absence of Gag, envelope fails to associate with DRMs. A mutation in the p17 matrix (L30E) domain in Gag (Gag L30E) that abrogates envelope incorporation onto virions also eliminated envelope association with DRMs in 293T cells and in the T-cell line, MOLT 4. These observations are consistent with a requirement for an Env-Gag interaction for raft association and subsequent assembly onto virions. In addition to this observation, we found that mutations in the gp41 cytoplasmic domain that abrogated envelope incorporation onto virions and impaired infectivity of cell-free virus also eliminated envelope association with DRMs. On the basis of these observations, we propose that Gag-envelope interaction is essential for efficient envelope association with DRMs, which in turn is essential for envelope budding and assembly onto virus particles.

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Available from: Alexander Repik, Jul 25, 2015
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    • "have been shown to carry bona fide raft marker proteins and HIV-1 Gag colocalizes with raft markers (Nguyen and Hildreth, 2000; Lindwasser and Resh, 2001; Ono and Freed, 2001; Bhattacharya et al., 2006). Furthermore, probing of membrane phase properties and fluidity revealed that the viral membrane is in a liquid-ordered-like state (Aloia et al., 1988; 1993; Lorizate et al., 2009). "
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    Cellular Microbiology 12/2012; 15(2). DOI:10.1111/cmi.12101 · 4.82 Impact Factor
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    • "Later, it was shown that Gag was responsible for the recruitment of Env to the lipid rafts (Bhattacharya et al., 2006; Patil et al., 2010) and that palmitoylation of cysteines was not involved (Chan et al., 2005). Indeed, deletion or mutation of Gag renders Env unable to localize to lipid rafts, limiting its incorporation into virions (Bhattacharya et al., 2006; Patil et al., 2010). Interaction with Gag and a membrane-proximal tyrosinebased motif overlapping the endocytosis motif in the CTT have also been shown to be important to polarized assembly and release of the virus (Deschambeault et al., 1999; Lodge et al., 1994, 1997). "
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    • "Apart from Gag, the interaction of other HIV proteins such as Env and Nef with lipid rafts is also important for the assembly of viral particles (Waheed and Freed 2009). However, Env appears to be associated with lipid rafts trough Gag interactions (Bhattacharya et al. 2006). For viral assembly to occur, Gag must be targeted to the plasma membrane, then multimerize and associate with other HIV proteins. "
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