Abstract
Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle.
Highlights
human immunodeficiency virus type 1 (HIV-1) Pr55Gag is composed of four structural domains named matrix (MA), capsid (CA), nucleocapsid (NC), p6, and two spacer peptides (p2 and p1) (Figure 1a) [16] and each of them carry Post translational modifications (PTMs)
These differences suggest that betaretroviruses have developed different strategies to sequester the myristoyl group until the virus-like particles (VLPs) is bound to the plasma membrane (PM)
Some retroviruses display a functional contribution of Ub modifications in virus release such as MLV, MPMV or RSV, and for those viruses, it was shown that, to what observed for HIV-1 [131], the inhibition of proteasome induces a reduction of the level of free Ubs in the cytoplasm, and impairs the release of the viral particles (Table 4) [127,132,133,142]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. PTMs play a key role in functional proteomic by regulating proteins activity, their localization, and the interaction with cellular or viral factors. It is not surprising that viruses developed different strategies to either counteract or exploit PTMs of cellular factors, and that many viral proteins carry PTMs. Interestingly, PTMs are strongly involved in the regulation of different steps of the retrovirus viral cycle (for reviews see [3,4]). Several pieces of evidence have shown that other retroviral Gag carry various PTMs regulate viral replication and pathogenesis. This review will summarize our current knowledge on PTMs observed in HIV-1 Pr55Gag and in other retroviral Gag proteins. Considering the role of the PMTs in the retroviral life cycle, the analysis of PTMs in retroviral Gag precursors could be important for a deeper understanding of the molecular mechanisms driving retroviral replication. This knowledge could contribute to the identification of new targets, and the design of new treatments against retroviral replication
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