Inhibition of Vif-Mediated Degradation of APOBEC3G through Competitive Binding of Core-Binding Factor Beta.
APOBEC-3G Deaminase
/ metabolism
Binding, Competitive
Core Binding Factor Alpha 2 Subunit
/ metabolism
Core Binding Factor beta Subunit
/ metabolism
Cullin Proteins
/ metabolism
Elongin
/ metabolism
Genes, Dominant
HEK293 Cells
HIV-1
/ physiology
Humans
Leukocytes, Mononuclear
/ metabolism
Mutation
Phenotype
Virion
vif Gene Products, Human Immunodeficiency Virus
/ metabolism
APOBEC3G
CBFβ
Vif
dominant-negative
interference
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
17 03 2020
17 03 2020
Historique:
received:
03
10
2019
accepted:
27
12
2019
pubmed:
17
1
2020
medline:
15
9
2020
entrez:
17
1
2020
Statut:
epublish
Résumé
Vif counteracts the host restriction factor APOBEC3G (A3G) and other APOBEC3s by preventing the incorporation of A3G into progeny virions. We previously identified Vif mutants with a dominant-negative (D/N) phenotype that interfered with the function of wild-type Vif, inhibited the degradation of A3G, and reduced the infectivity of viral particles by increased packaging of A3G. However, the mechanism of interference remained unclear, in particular since all D/N Vif mutants were unable to bind Cul5 and some mutants additionally failed to bind A3G, ruling out competitive binding to A3G or the E3 ubiquitin ligase complex as the sole mechanism. The goal of the current study was to revisit the mechanism of D/N interference by Vif mutants and analyze the possible involvement of core binding factor beta (CBFβ) in this process. We found a clear correlation of D/N properties of Vif mutants with their ability to engage CBFβ. Only mutants that retained the ability to bind CBFβ exhibited the D/N phenotype. Competition studies revealed that D/N Vif mutants directly interfered with the association of CBFβ and wild-type Vif. Furthermore, overexpression of CBFβ counteracted the interference of D/N Vif mutants with A3G degradation by wild-type Vif. Finally, overexpression of Runx1 mimicked the effect of D/N Vif mutants and inhibited the degradation of A3G by wild-type Vif. Taken together, we identified CBFβ as the key player involved in D/N interference by Vif.
Identifiants
pubmed: 31941780
pii: JVI.01708-19
doi: 10.1128/JVI.01708-19
pmc: PMC7081906
pii:
doi:
Substances chimiques
CBFB protein, human
0
CUL5 protein, human
0
Core Binding Factor Alpha 2 Subunit
0
Core Binding Factor beta Subunit
0
Cullin Proteins
0
ELOB protein, human
0
Elongin
0
RUNX1 protein, human
0
vif Gene Products, Human Immunodeficiency Virus
0
vif protein, Human immunodeficiency virus 1
0
APOBEC-3G Deaminase
EC 3.5.4.5
APOBEC3G protein, human
EC 3.5.4.5
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Intramural NIH HHS
ID : Z01 AI000669
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Microbiology.
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