Jaguva Vasudevan, AA, Mario, P, Bulliard, Y, Cichutek, K, Trono, D, Haussinger, D and Munk, C (2013) Prototype foamy virus bet impairs the dimerization and cytosolic solubility of human APOBEC3G. Journal of Virology. pp. 9030-9040.

Abstract

Cellular cytidine deaminases from the APOBEC3 family are potent restriction factors that are able to block the replication of retroviruses. Consequently, retroviruses have evolved a variety of different mechanisms to counteract inhibition by APOBEC3 proteins. Lentiviruses such as human immunodeficiency virus (HIV) express Vif, which interferes with APOBEC3 proteins by targeting these restriction factors for proteasomal degradation, hence blocking their ability to access the reverse transcriptase complex in the virions. Other retroviruses use less-well-characterized mechanisms to escape the APOBEC3-mediated cellular defense. Here we show that the prototype foamy virus Bet protein can protect foamy viruses and an unrelated simian immunodeficiency virus against human APOBEC3G (A3G). In our system, Bet binds to A3G and prevents its encapsidation without inducing its degradation. Bet failed to coimmunoprecipitate with A3G mutants unable to form homodimers and dramatically reduced the recovery of A3G proteins from soluble cytoplasmic cell fractions. The Bet-A3G interaction is probably a direct binding interaction and seems to be independent of RNA. Together, these data suggest a novel model whereby Bet uses two possibly complementary mechanisms to counteract A3G: (i) Bet prevents encapsidation of A3G by blocking A3G dimerization, and (ii) Bet sequesters A3G in immobile complexes, impairing its ability to interact with nascent virions. 2013, American Society for Microbiology

Item Type:	Article
Additional Information:	pubid: 184 nvp_institute: NIBR contributor_address: (Jaguva Vasudevan, Mario Perkovic, Haussinger, Munk) Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich Heine University, Dusseldorf, Germany (Mario Perkovic, Cichutek) Division of Medical Biotechnology, Paul Ehrlich Institut, Langen, Germany (Bulliard, Trono) School of Life Sciences and Frontiers-in-Genetics National Program, Ecole Polytechnique Fe;de;rale de Lausanne (EPFL), Lausanne, Switzerland (Mario Perkovic) Institute for Biophysics and Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe University, Frankfurt, Germany (Bulliard) Novartis, Novartis Institutes for Biomedical Research, Cambridge, MA, United States
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22005