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Nucleic Acids Res. 2006 Jan 10;34(1):89-95. Print 2006.

APOBEC3A and APOBEC3B are potent inhibitors of LTR-retrotransposon function in human cells.

Author information

1
Center for Virology and Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.

Abstract

While the ability of APOBEC3G to reduce the replication of a range of exogenous retroviruses is now well established, recent evidence has suggested that APOBEC3G can also inhibit the replication of endogenous retrotransposons that bear long terminal repeats. Here, we extend this earlier work by showing that two other members of the human APOBEC3 protein family, APOBEC3B and APOBEC3A, can reduce retrotransposition by the intracisternal A-particle (IAP) retrotransposon in human cells by 20-fold to up to 100-fold, respectively. This compares to an approximately 4-fold inhibition in IAP retrotransposition induced by APOBEC3G. While both APOBEC3G and APOBEC3B specifically interact with the IAP Gag protein in co-expressing cells, and induce extensive editing of IAP reverse transcripts, APOBEC3A fails to package detectably into IAP virus-like particles and does not edit IAP reverse transcripts. These data, which identify human APOBEC3A as a highly potent inhibitor of LTR-retrotransposon function, are the first to ascribe a biological activity to APOBEC3A. Moreover, these results argue that APOBEC3A inhibits IAP retrotransposition via a novel mechanism that is distinct from, and in this case more effective than, the DNA editing mechanism characteristic of APOBEC3G and APOBEC3B.

PMID:
16407327
PMCID:
PMC1326241
DOI:
10.1093/nar/gkj416
[Indexed for MEDLINE]
Free PMC Article

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