Positionally independent and exchangeable late budding functions of the Rous sarcoma virus and human immunodeficiency virus Gag proteins

Abstract

The Gag proteins of Rous sarcoma virus and human immunodeficiency virus (HIV) each contain a function involved in a late step in budding, defects in which result in the accumulation of these molecules at the plasma membrane. In the Rous sarcoma virus Gag protein (Pr76 gag), this assembly domain is associated with a PPPY motif, which is located at an internal position between the MA and CA sequences. This motif is not contained anywhere within the HIV Gag protein (Pr55 gag), and the MA sequence is linked directly to CA. Instead, a late assembly function of HIV has been associated with the p6 sequence situated at the C terminus of Gag. Here we demonstrate the remarkable finding that the late assembly domains from these two unrelated Gag proteins are exchangeable between retroviruses and can function in a positionally independent manner.

TIP47 is Required for the Production of Infectious HIV-1 Particles from Primary Macrophages

“…The binding of Gag to TIP47 could favour HIV-1 assembly and/or sequestration in CD53-, CD9-and CD81-enriched plasma-derived internal compartment of macrophages previously characterized (10,19,20) through the recruitment of cellular cofactors abundant in this area. Since TIP47-binding region in MA overlaps a region implicated in Gag anchoring and binding at the plasma membrane (41,42), we could not exclude that the MA WE-AA mutation inhibiting Gag/TIP47 interaction may modulate Gag-binding affinity for the plasma membrane, and thus redistribute the MA labelling at or close to the surface of infected macrophages, resulting in the increased HIV-1 release observed in our production assays (Table 1, release of MA WE-AA mutant). This data, taken together with the results of a recent study (43) highlight the fact that macrophages are very plastic cells in which HIV-1 productive assembly can take place at different locations (i.e.…”

The Ubiquitin-Conjugating System: Multiple Roles in Viral Replication and Infection

“…Interestingly, the PPXY type of L-domain interacts with the members of the Nedd4-like family of ubiquitin ligases by directly binding the WW domain characteristic of these cellular proteins [183]. Finally, the L-domains act independently from their position in the viral protein, frequently occur in combination and can be exchanged between unrelated viruses without losing their ability to mediate budding [188][189][190][191][192]. Overall, these features are suggestive of a role for the L-domains as docking sites for cellular factors belonging to a specific pathway involving Ub and exploited by retroviruses to efficiently execute budding.…”

New insights into the nuclear localization of retroviral gag proteins

“…5,50 Release of virus particles is controlled by the "L" (late) domain by recruiting host machinery, including endosomal sorting factors. 12,16,42 In addition to the essential assembly domains, RSV Gag contains targeting motifs that control its intracellular trafficking. 7,46 It was previously thought that for clinical use.…”