Species-specific inhibition of APOBEC3C by the prototype foamy virus protein bet.
The APOBEC3 cytidine deaminases are part of the intrinsic defense of cells against retroviruses. Lentiviruses and spumaviruses have evolved essential accessory proteins, Vif and Bet, respectively, which counteract the APOBEC3 proteins. We show here that Bet of the Prototype foamy virus inhibits the antiviral APOBEC3C activity by a mechanism distinct to Vif: Bet forms a complex with APOBEC3C without inducing its degradation. Bet abolished APOBEC3C dimerization as shown by coimmunoprecipitation and cross-linking experiments. These findings implicate a physical interaction between Bet and the APOBEC3C. Subsequently, we identified the Bet interaction domain in human APOBEC3C in the predicted APOBEC3C dimerization site. Taken together, these data support the hypothesis that Bet inhibits incorporation of APOBEC3Cs into retroviral particles. Bet likely achieves this by trapping APOBEC3C protein in complexes rendering them unavailable for newly generated viruses due to direct immobilization.
Perkovic
Mario
M
Division of Medical Biotechnology, Paul-Ehrlich-Institut, Langen 63225, Germany.
Schmidt
Stanislaw
S
Marino
Daniela
D
Russell
Rebecca A
RA
Stauch
Benjamin
B
Hofmann
Henning
H
Kopietz
Ferdinand
F
Kloke
Björn-Philipp
BP
Zielonka
Jörg
J
Ströver
Heike
H
Hermle
Johannes
J
Lindemann
Dirk
D
Pathak
Vinay K
VK
Schneider
Gisbert
G
Löchelt
Martin
M
Cichutek
Klaus
K
Münk
Carsten
C
D000071480:APOBEC-3G Deaminase; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003432:Cross-Linking Reagents; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D019281:Dimerization; D016346:Gene Products, vif / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008253:Macaca mulatta; D008254:Macaca nemestrina; D002679:Pan troglodytes; D011533:Proviruses / Q000235:genetics*; D012191:Retroviridae Proteins / Q000502:physiology*; D053150:Simian foamy virus; D014162:Transfection; D019065:Virus Assembly; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D003432:Cross-Linking Reagents; D016346:Gene Products, vif; D012191:Retroviridae Proteins; C080099:bet protein, human foamy virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase