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Nucleic Acids Res. 2008 Dec;36(21):6859-71. doi: 10.1093/nar/gkn802. Epub 2008 Oct 29.

The antiretroviral potency of APOBEC1 deaminase from small animal species.

Author information

1
Department of Retrovirology and Self-Defense, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

Although the role of the APOBEC3-dependent retroelement restriction system as an intrinsic immune defense against human immunodeficiency virus type1 (HIV-1) infection is becoming clear, only the rat ortholog of mammalian APOBEC1s (A1) thus far has been shown to possess antiviral activity. Here, we cloned A1 cDNAs from small animal species, and showed that similar to rat A1, both wild-type and Deltavif HIV-1 infection was inhibited by mouse and hamster A1 (4- to 10-fold), whereas human A1 had negligible effects. Moreover, rabbit A1 significantly reduced the infectivity of both HIV-1 virions (>300-fold), as well as that of SIVmac, SIVagm, FIV and murine leukemia virus. Immunoblot analysis showed that A1s were efficiently incorporated into the HIV-1 virion, and their packaging is mediated through an interaction with the nucleocapsid Gag domain. Interestingly, there was a clear accumulation of particular C-T changes in the genomic RNAs of HIV-1 produced in their presence, with few G-A changes in the proviral DNA. Together, these data reveal that A1 may function as a defense mechanism, regulating retroelements in a wide range of mammalian species.

PMID:
18971252
PMCID:
PMC2588513
DOI:
10.1093/nar/gkn802
[Indexed for MEDLINE]
Free PMC Article

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