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Nucleic Acids Research Advance Access originally published online on October 29, 2008
Nucleic Acids Research 2008 36(21):6859-6871; doi:10.1093/nar/gkn802
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Nucleic Acids Research, 2008, Vol. 36, No. 21 6859-6871
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

The antiretroviral potency of APOBEC1 deaminase from small animal species

Terumasa Ikeda1,2, Takeo Ohsugi3, Tetsuya Kimura1, Shuzo Matsushita4, Yosuke Maeda2, Shinji Harada2 and Atsushi Koito1,*

1Department of Retrovirology and Self-Defense, Faculty of Medical and Pharmaceutical Sciences, 2Department of Medical Virology, Faculty of Medical and Pharmaceutical Sciences, 3Center for Animal Resources and Development, Institute of Resource Development and Analysis and 4Center for AIDS Research, Kumamoto University, Kumamoto 860-8556, Japan

*To whom correspondence should be addressed. Tel: +81 96 373 5133; Fax: +81 96 373 5132; Email: akoito{at}kumamoto-u.ac.jp

Received August 28, 2008. Revised October 7, 2008. Accepted October 11, 2008.

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 {Delta}vif 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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