TY - JOUR
T1 - Post-translational modifications inducing proteasomal degradation to counter HIV-1 infection
AU - Proulx, Jessica
AU - Borgmann, Kathleen
AU - Park, In Woo
N1 - Publisher Copyright:
© 2020
PY - 2020/11
Y1 - 2020/11
N2 - Post-translational modifications (PTMs) are integral to regulating a wide variety of cellular processes in eukaryotic cells, such as regulation of protein stability, alteration of celluar location, protein activity modulation, and regulation of protein interactions. HIV-1, like other eukaryotic viruses, and its infected host exploit the proteasomal degradation system for their respective proliferation and survival, using various PTMs, including but not limited to ubiquitination, SUMOylation, NEDDylation, interferon-stimulated gene (ISG)ylation. Essentially all viral proteins within the virions -- and in the HIV-1-infected cells -- interact with their cellular counterparts for this degradation, utilizing ubiquitin (Ub), and the Ub-like (Ubl) modifiers less frequently, to eliminate the involved proteins throughout the virus life cycle, from the entry step to release of the assembled virus particles. Such interplay is pivotal for, on the one hand, the cell to restrict proliferation of the infecting virus, and on the other, for molecular counteraction by the virus to overcome this cellular protein-imposed restriction. Recent reports indicate that not only viral/cellular proteins but also viral/viral protein interactions play vital roles in regulating viral protein stability. We hence give an overview of the molecular processes of PTMs involved in proteasomal degradation of the viral and cellular proteins, and the viral/viral and viral/cellular protein interplay in restriction and competition for HIV-1 vs. host cell survival. Insights in this realm could open new avenues for developing therapeutics against HIV-1 via targeting specific steps of the proteasome degradation pathway during the HIV-1 life cycle.
AB - Post-translational modifications (PTMs) are integral to regulating a wide variety of cellular processes in eukaryotic cells, such as regulation of protein stability, alteration of celluar location, protein activity modulation, and regulation of protein interactions. HIV-1, like other eukaryotic viruses, and its infected host exploit the proteasomal degradation system for their respective proliferation and survival, using various PTMs, including but not limited to ubiquitination, SUMOylation, NEDDylation, interferon-stimulated gene (ISG)ylation. Essentially all viral proteins within the virions -- and in the HIV-1-infected cells -- interact with their cellular counterparts for this degradation, utilizing ubiquitin (Ub), and the Ub-like (Ubl) modifiers less frequently, to eliminate the involved proteins throughout the virus life cycle, from the entry step to release of the assembled virus particles. Such interplay is pivotal for, on the one hand, the cell to restrict proliferation of the infecting virus, and on the other, for molecular counteraction by the virus to overcome this cellular protein-imposed restriction. Recent reports indicate that not only viral/cellular proteins but also viral/viral protein interactions play vital roles in regulating viral protein stability. We hence give an overview of the molecular processes of PTMs involved in proteasomal degradation of the viral and cellular proteins, and the viral/viral and viral/cellular protein interplay in restriction and competition for HIV-1 vs. host cell survival. Insights in this realm could open new avenues for developing therapeutics against HIV-1 via targeting specific steps of the proteasome degradation pathway during the HIV-1 life cycle.
KW - HIV-1
KW - Post-translational modification
KW - Proteasomal degradation
KW - Ubiquitin and ubiquitin-like modifiers
KW - Ubiquitin proteasome system
UR - http://www.scopus.com/inward/record.url?scp=85090183173&partnerID=8YFLogxK
U2 - 10.1016/j.virusres.2020.198142
DO - 10.1016/j.virusres.2020.198142
M3 - Review article
C2 - 32882242
AN - SCOPUS:85090183173
SN - 0168-1702
VL - 289
JO - Virus Research
JF - Virus Research
M1 - 198142
ER -