title: Prototype foamy virus Bet impairs the dimerization and cytosolic solubility of human APOBEC3G.
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.
authors.affiliation: Clinic for Gastroenterology, Hepatology, and Infectiology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Ananda Ayyappan
authors.initials: AA
authors.lastname: Jaguva Vasudevan
authors.forename: Mario
authors.initials: M
authors.lastname: Perkovic
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bulliard
authors.forename: Klaus
authors.initials: K
authors.lastname: Cichutek
authors.forename: Didier
authors.initials: D
authors.lastname: Trono
authors.forename: Dieter
authors.initials: D
authors.lastname: Häussinger
authors.forename: Carsten
authors.initials: C
authors.lastname: Münk
mesh_terms: D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D055503:Protein Multimerization; D012191:Retroviridae Proteins / Q000378:metabolism*; D053150:Simian foamy virus / Q000276:immunology*; D012995:Solubility; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D012191:Retroviridae Proteins; D037521:Virulence Factors; C080099:bet protein, human foamy virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase