Disease relevance of gag

• N-terminal Gag domain required for foamy virus particle assembly and export [1].
• Compared to conventional retroviruses, which require only Gag proteins for budding and release of virus-like particles (VLPs), both FV and HBV require Env proteins [2].
• The capsids were surrounded by an internal Gag layer that in turn was surrounded by, and separated from, the viral membrane [3].
• Using a transient FV vector transfection system, it is shown that pregenomic RNA is required for efficient virion incorporation of functionally active Pol and that protein-protein interactions of Pol with Gag are not sufficient to complete particle assembly [4].
• A virus lacking the Gag nuclear localization signal accumulates fewer proviruses, suggesting that nuclear translocation is important for high proviral load [5].

High impact information on gag

• In contrast, the Pol protein of HFV is translated from a spliced messenger RNA and lacks Gag domains [6].
• Although WT Bet efficiently preserved FFV infectivity and genome integrity, it sustained particle release and Gag processing only when fe3 was moderately expressed [7].
• Foamy viruses (FV) are unusual among retroviruses since they require both Gag and Env structural proteins for particle egress [8].
• Furthermore, at position 50, this region harbors the conserved arginine that is presumably at the center of a signal sequence directing FV Gag proteins to a cytoplasmic assembly site [1].
• However, whereas nuclear import of Gag and of the viral genome was observed for the wild-type virus as early as 8 hours postinfection, incoming capsids and genome from mutant viruses remained at the MTOC [9].

Biological context of gag

• Assembly of retroviral particles containing RNA genomes requires only the Gag structural protein [10].
• The transmembrane protein Elp specifically interacts with N-terminal Gag sequences during morphogenesis [11].
• Here, we identify a discrete approximately 151-nucleotide sequence, located within the R region of the HFV long terminal repeat, that activates HFV Gag and Pol expression when present in the 5' noncoding region but that is inactive when inverted or when placed in the 3' noncoding region [12].
• The purified N-terminal domain of FFV Gag specifically interacted with synthetic peptides and a defined protein domain derived from the N-terminal Env leader protein [3].
• To more thoroughly characterize the important sequence features and properties of I domains, we analyzed Gag proteins that contain one or no zinc finger motifs [13].

Anatomical context of gag

• While EFV Gag was detected in both the cytoplasm and the nucleus, EFV Env mainly localized in the Golgi complex, in contrast to HFV Env, which is sequestered in the endoplasmic reticulum [14].
• The results also showed that addition of a Myr-membrane targeting signal to the C-terminus of Gag could restore the budding from plasma membrane, implying that Myr-membrane targeting signal could substitute for Env protein in budding [15].
• We also explored the possibility that differences in I domains (e.g., their number) account for differences in the ability of Gag proteins to be rescued into particles when they are unable to bind to membranes [13].
• Analyzing the intracellular localization of incoming foamy viruses, we have found that the Gag antigens and the viral genome accumulate in a distinct perinuclear domain identified as the centrosome [16].
• Rather than being a defective viral protease function, an association of Gag precursors with a cytoskeleton network might be responsible for the low rate of Gag protein maturation through inhibition of their cleavage by the protease [17].

Associations of gag with chemical compounds

• Oligopeptides that correspond to proteolytic cleavage site junctions of the native Gag and Pol proteins are specifically cleaved by retroviral aspartate proteases (PRs) [18].
• Western blot analyses of preassembled HFV cores isolated from the cytoplasm of infected cells and purified by sucrose gradient centrifugation demonstrated the presence of Pr78gag/74gag and Pr135pol, but no proteolytically processed Gag proteins were observed [19].

Other interactions of gag

• At the protein level, the use of specific antibodies allowed us to determine the size and the subcellular localization of EFV Gag, Env, and Tas, the viral transactivators [14].

Analytical, diagnostic and therapeutic context of gag

• Biochemical and electron microscopy analysis demonstrated that these mutant particles incorporated all viral structural proteins but contained aberrantly capsid structures, suggesting a role in capsid assembly for this PFV Gag sequence motif [8].
• To delineate the proteolytic cleavage sites between potential Gag subdomains, recombinant human spumaretrovirus (HSRV) Gag proteins of different lengths were expressed, purified by affinity chromatography, and subjected to HSRV protease assays [20].
• Spumaviruses, or foamy viruses, express Gag proteins that are incompletely processed by the viral protease in cell cultures [20].
• We screened first plasma or sera of the animals with a Western blot detecting the SFVs Gag doublet proteins [21].

References