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Publication : The antiretroviral potency of APOBEC1 deaminase from small animal species.

First Author  Ikeda T Year  2008
Journal  Nucleic Acids Res Volume  36
Issue  21 Pages  6859-71
PubMed ID  18971252 Mgi Jnum  J:173048
Mgi Id  MGI:5009509 Doi  10.1093/nar/gkn802
Citation  Ikeda T, et al. (2008) The antiretroviral potency of APOBEC1 deaminase from small animal species. Nucleic Acids Res 36(21):6859-71
abstractText  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.
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