The HIV-1 Vif PPLP motif is necessary for human APOBEC3G binding and degradation.
The HIV-1 virion infectivity factor (Vif) is required during viral replication to inactivate the host cell anti-viral factor, APOBEC3G (A3G). Vif binds A3G and a Cullin5-ElonginBC E3 ubiquitin ligase complex which results in the proteasomal degradation of A3G. The Vif PPLP motif (amino acids 161-164) is essential for normal Vif function because mutations in this motif reduce the infectivity of virions produced in T-cells. In this report, we demonstrate that mutation of the Vif PPLP motif reduces Vif binding to A3G without affecting its interaction with ElonginC and Cullin5. We demonstrate that the failure of the Vif mutant to bind A3G resulted in A3G incorporation into assembling virions with loss of viral infectivity.
Donahue
John P
JP
Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, A-2200, Medical Center North, Nashville, TN 37232, USA. john.donahue@vanderbilt.edu
Vetter
Michael L
ML
Mukhtar
Nizar A
NA
D'Aquila
Richard T
RT
D000071480:APOBEC-3G Deaminase; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D044842:Cullin Proteins / Q000737:chemistry / Q000378:metabolism; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000075065:Elongin; D005816:Genetic Complementation Test; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D046912:Multiprotein Complexes; D009154:Mutation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
C496871:CUL5 protein, human; D044842:Cullin Proteins; D000075065:Elongin; D046912:Multiprotein Complexes; D014157:Transcription Factors; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D046988:Proteasome Endopeptidase Complex; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase