Author/Editor		Aguiar, Renato S; Lovšin, Nika; Tanuri, Amilcar; Peterlin, Mitja B
Title		Vpr.A3A chimera inhibits HIV replication
Type		članek
Source		J Biol Chem
Vol. and No.		Letnik 283, št. 5
Publication year		2008
Volume		str. 2518-25
Language		eng
Abstract		Several APOBEC3 proteins (A3F and A3G), that are cytidine deaminases restrict human immunodeficiency virus (HIV) replication in the absence of the viral infectivity factor (Vif) protein. However, Vif leads to their degradation and counteracts their effects. Another member, A3A, restricts some retrotransposons and another virus but not HIV. We reasoned that this failure was due to the lack of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr.A3A chimera but not A3A was found abundantly in the viral core. It also restricted potently the replication of HIV and simian immunodeficiency virus in the presence and absence of Vif. Because we identified a high frequency of G to A mutations in viral cDNAs, this antiviral activity was mediated by DNA editing. Interestingly, our fusion protein did not restrict murine leukemia virus, which does not incorporate Vpr. Thus, by targeting appropriately a potent single domain cytidine deaminase, we rendered HIV and simian immunodeficiency virus restriction resistant to Vif.
Descriptors		BASE SEQUENCE CELL LINE CYTIDINE DEAMINASE DNA PRIMERS DNA, VIRAL GENE PRODUCTS, VIF HIV PROTEINS RECOMBINANT FUSION PROTEINS VIRUS REPLICATION