Species-specific inhibition of APOBEC3C by the prototype foamy virus protein bet

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Mario Perkovic - (Autor:in)
  • Stanislaw Schmidt - (Autor:in)
  • Daniela Marino - (Autor:in)
  • Rebecca A Russell - (Autor:in)
  • Benjamin Stauch - (Autor:in)
  • Henning Hofmann - (Autor:in)
  • Ferdinand Kopietz - (Autor:in)
  • Björn-Philipp Kloke - (Autor:in)
  • Jörg Zielonka - (Autor:in)
  • Heike Ströver - (Autor:in)
  • Johannes Hermle - (Autor:in)
  • Dirk Lindemann - , Institut für Medizinische Mikrobiologie und Virologie (Autor:in)
  • Vinay K Pathak - (Autor:in)
  • Gisbert Schneider - (Autor:in)
  • Martin Löchelt - (Autor:in)
  • Klaus Cichutek - (Autor:in)
  • Carsten Münk - (Autor:in)

Abstract

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)5819-26
Seitenumfang8
FachzeitschriftThe Journal of biological chemistry
Jahrgang284
Ausgabenummer9
PublikationsstatusVeröffentlicht - 27 Feb. 2009
Peer-Review-StatusJa

Externe IDs

PubMedCentral PMC2645832
ORCID /0000-0002-0320-4223/work/150885080
Scopus 65549126392

Schlagworte

Schlagwörter

  • APOBEC-3G Deaminase, Animals, Cells, Cultured, Chlorocebus aethiops, Cricetinae, Cross-Linking Reagents, Cytidine Deaminase/antagonists & inhibitors, Dimerization, Gene Products, vif/physiology, Humans, Immunoblotting, Immunoprecipitation, Kidney/cytology, Lentivirus/genetics, Macaca mulatta, Macaca nemestrina, Pan troglodytes, Proviruses/genetics, Retroviridae Proteins/physiology, Simian foamy virus, Transfection, Virus Assembly, Virus Replication/drug effects