Targeting of Murine Leukemia Virus Gag to the Plasma Membrane Is Mediated by PI(4,5)P
            <sub>2</sub>
            /PS and a Polybasic Region in the Matrix

Hamard-Péron, Élise; Juillard, Franceline; Saad, Jamil S.; Roy, Christian; Roingeard, Philippe; Summers, Michael F.; Darlix, Jean‐Luc; Picart, Catherine; Muriaux, Delphine

doi:10.1128/jvi.01134-09

Cited by 79 publications

(103 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MA domain of Gag contains a bipartite signal that promotes stable interaction with the plasma membrane: a N-terminal myristyl group and a patch of basic residues within MA that interacts specifically with PI(4,5)P 2 , a class of phospholipids that resides exclusively in the plasma membrane. [65][66][67] What was less clear until recently is how the viral genome is recruited to assembly sites. Characterization of the localization of two lentiviral genomes in live cells, in the presence or absence of Gag, revealed that Gag is responsible for the recruitment of the genome to the plasma membrane 61,68 ( Fig.…”

Section: Cellular Site(s) Of Initial Recognition Of Rna By Gagmentioning

confidence: 99%

Cell biology of retroviral RNA packaging

et al. 2011

View full text Add to dashboard Cite

Section: Cellular Site(s) Of Initial Recognition Of Rna By Gagmentioning

confidence: 99%

Cell biology of retroviral RNA packaging

et al. 2011

View full text Add to dashboard Cite

“…4), indicating that MA is required for Gag recruitment to cell-cell contact sites. Likewise, when MA was deleted and MLV Gag targeted to the plasma membrane using the PH domain of PLC␦ that binds PIP2 (11,21,36), MLV Gag failed to be recruited to sites of cell-cell contact (Fig. 4).…”

mentioning

confidence: 99%

Viral Determinants of Polarized Assembly for the Murine Leukemia Virus

Jin

Mothes

2011

J Virol

View full text Add to dashboard Cite

Retrovirus transmission via direct cell-cell contact is more efficient than diffusion through the extracellular milieu. This is believed to be due to the ability of viruses to efficiently coordinate several steps of the retroviral life cycle at cell-cell contact sites (D. Viruses exploit and manipulate cell-cell contacts for efficient spreading (12,18,32,37,43). In the case of the human immunodeficiency virus (HIV) and the human T cell lymphoma virus these cell-cell contacts share features with immunological synapses and have been designated infectious or virological synapses (13,14,19,29,41). Using the murine leukemia virus (MLV) as a model system, we demonstrated that the interaction between the viral Env glycoprotein (Env), expressed on the infected cell and the viral receptor, expressed on the uninfected target cell, leads to the establishment of cell-cell contacts (32, 45). Importantly, following the establishment of cellcell adhesion, assembly was polarized toward the cell-cell contact (16). These data suggested that the infected cell can "sense" the uninfected cell and direct the viral components needed to assemble viruses toward the uninfected cell. Sensing of the target cell turned out to be mediated by the accumulation of Env and receptor at the cell-cell interface and depending on the presence of a cytoplasmic tail (C-tail) of Env, MLV Gag was recruited toward the site of cell-cell contact. Here, we identify a tyrosine residue within the C-tail of Env and matrix within Gag as the viral determinants responsible for this process.C MATERIALS AND METHODSPlasmids and reagents. Mutant MLV envelope expression vectors were generated by site-directed mutagenesis based on the Friend MLV envelope expression vector previously described (16,46). MLV Gag-GFP expression vector was made by fusing enhanced green fluorescent protein (eGFP) to C-terminal of Gag and deleting a large fragment of Pol in full-length Friend57 MLV expression vector pLRB303 (23,35). Individual domains of MLV Gag-GFP were deleted or replaced by a standard overlapping PCR approach. MLV Gag-YFP expression vector was previously described (46). Chimeric MLV Gag with MA swapped with HIV MA was kindly provided by Marc Johnson, University of Missouri. HIV Gag-GFP expression vector and chimeric HIV Gag with MA swapped with MLV MA were described previously (17). HEK293 and XC cells were previously described (16).Visualizing virus cell-to-cell transmission. HEK293 cells were transfected with indicated plasmids by FuGENE 6 and cocultured 4 h posttransfection with XC cells expressing mCherry or cyan fluorescent protein (CFP)-tagged mCAT-1 as previously described (16). The formation of MLV synapses was reproducibly observed 2 to 6 postinitiation of cocultures for MLV generated by the tripartite system (MLV GagPol, Gag-YFP, MLV LTR, and MLV Env) or 4 to 10 h postinitiation of cocultures for MLV generated using proviral pLRB303-derived constructs. Imaging of fixed samples, as well as live-cell imaging, was performed using spinning disc confocal microscopy as ...

show abstract

“…In contrast, basic residues in MA are required for Gag membrane binding via their interactions with the phosphinositide PI(4,5)P2. [99][100][101] In addition for HIV-1, these MA basic residues are also a site for gRNA binding. Thus, it was proposed that RNA would serve as a regulator of Gag assembly.…”

mentioning

confidence: 99%