Inhibition of a yeast LTR retrotransposon by human APOBEC3 cytidine deaminases.
The mammalian APOBEC3 family of cytidine deaminases includes several members that possess potent antiretroviral activity. Human APOBEC3F and APOBEC3G are specifically incorporated into human immunodeficiency virus type 1 (HIV-1) progeny virions in the absence of virion infectivity factor (Vif), where they deaminate deoxycytidine to deoxyuridine on the minus strand of nascent reverse transcripts. Editing of the HIV-1 cDNA leads to its degradation or to G to A hypermutation of the integrated provirus. Here, we show that APOBEC3 proteins also restrict the activity of a distantly related long terminal repeat (LTR) retrotransposon. When expressed in the yeast Saccharomyces cerevisiae, human APOBEC3C, APOBEC3F, or APOBEC3G or mouse APOBEC3 potently inhibit replication of the Ty1 LTR retrotransposon. APOBEC3G interacts with Ty1 Gag and is packaged into Ty1 virus-like particles (VLPs) by a mechanism that closely resembles the one it uses to enter HIV-1 virions. Expression of APOBEC3G results in a reduced level of Ty1 cDNA integration and G to A editing of integrated Ty1 cDNA. Our findings indicate that APOBEC3G restricts Ty1 and HIV-1 by similar mechanisms and suggest that the APOBEC3 proteins target a substantially broader spectrum of retroelements than previously appreciated.
Dutko
James A
JA
Laboratory of Developmental Genetics, Wadsworth Center and Department of Biomedical Sciences, University at Albany, P.O. Box 22002, Albany, New York 12201, USA.
Schäfer
Alexandra
A
Kenny
Alison E
AE
Cullen
Bryan R
BR
Curcio
M Joan
MJ
D000071480:APOBEC-3G Deaminase; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003564:Cytidine Deaminase; D017931:DNA Primers; D004261:DNA Replication / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D015751:Genes, pol / Q000235:genetics; D005982:Glutathione Transferase; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice / Q000235:genetics; D005810:Multigene Family / Q000235:genetics; D009700:Nucleoside Deaminases; D010957:Plasmids / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins; D018626:Retroelements / Q000235:genetics*; D012441:Saccharomyces cerevisiae; D017422:Sequence Analysis, DNA
D017931:DNA Primers; D018076:DNA, Complementary; D011506:Proteins; D012097:Repressor Proteins; D018626:Retroelements; D005982:Glutathione Transferase; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase