Species-specific Inhibition of APOBEC3C by the Prototype Foamy Virus Protein Bet

被引：62

作者：

Perkovic, Mario ^{[1
]}

Schmidt, Stanislaw ^{[1
]}

Marino, Daniela ^{[1
]}

Russell, Rebecca A. ^{[2
]}

Stauch, Benjamin ^{[3
]}

Hofmann, Henning ^{[1
,6
]}

Kopietz, Ferdinand ^{[1
]}

Kloke, Bjoern-Philipp ^{[1
]}

Zielonka, Joerg ^{[1
,6
]}

Stroever, Heike ^{[1
]}

Hermle, Johannes ^{[1
]}

Lindemann, Dirk ^{[4
]}

Pathak, Vinay K. ^{[2
]}

Schneider, Gisbert ^{[3
]}

Loechelt, Martin ^{[5
]}

Cichutek, Klaus ^{[1
]}

Muenk, Carsten ^{[1
,6
]}

机构：

[1] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany

[2] NCI, HIV Drug Resistance Program, NIH, Ctr Canc Res, Frederick, MD 21702 USA

[3] Univ Frankfurt, Inst Organ Chem & Chem Biol, D-60323 Frankfurt, Germany

[4] Tech Univ Dresden, Inst Virol, D-01307 Dresden, Germany

[5] German Canc Res Ctr, Res Program Infect & Canc, Dept Genome Modificat & Carcinogenesis, D-69120 Heidelberg, Germany

[6] Univ Dusseldorf, Clin Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2009年 / 284卷 / 09期

基金：

美国国家卫生研究院;

关键词：

EDITING ENZYME APOBEC3G; TYPE-1; VIF; HIV-1; ANTIRETROVIRAL DEFENSE; CYTIDINE DEAMINASES; ANTIVIRAL ACTIVITY; LEUKEMIA-VIRUS; MURINE APOBEC3; DISTINCT; SOCS-BOX;

D O I：

10.1074/jbc.M808853200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 co-immunoprecipitation 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.

引用

页码：5819 / 5826

页数：8

共 62 条

[1] Murine retrovirus escapes from murine APOBEC3 via two distinct novel mechanisms [J].