Báo cáo y học: APOBEC3G targets human T-cell leukemia virus type 1

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Báo cáo y học: " APOBEC3G targets human T-cell leukemia virus type 1"Retrovirology BioMed Central Open AccessResearchAPOBEC3G targets human T-cell leukemia virus type 1Amane Sasada1, Akifumi Takaori-Kondo*1, Kotaro Shirakawa1,Masayuki Kobayashi1, Aierkin Abudu1, Masakatsu Hishizawa1,Kazunori Imada1, Yuetsu Tanaka2 and Takashi Uchiyama1Address: 1Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto606-8507, Japan and 2Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, JapanEmail: Amane Sasada - amasasa@kuhp.kyoto-u.ac.jp; Akifumi Takaori-Kondo* - atakaori@kuhp.kyoto-u.ac.jp;Kotaro Shirakawa - kotash@kuhp.kyoto-u.ac.jp; Masayuki Kobayashi - sailing@kuhp.kyoto-u.ac.jp;Aierkin Abudu - abdiriyimarkin@yahoo.co.jp; Masakatsu Hishizawa - hishiza@kuhp.kyoto-u.ac.jp; Kazunori Imada - imadak@kuhp.kyoto-u.ac.jp; Yuetsu Tanaka - yuetsu@ma.kcom.ne.jp; Takashi Uchiyama - uchiyata@kuhp.kyoto-u.ac.jp* Corresponding authorPublished: 19 May 2005 Received: 21 April 2005 Accepted: 19 May 2005Retrovirology 2005, 2:32 doi:10.1186/1742-4690-2-32This article is available from: http://www.retrovirology.com/content/2/1/32© 2005 Sasada et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is a host cellular protein with a broad antiviral activity. It inhibits infectivitiy of a wide variety of retroviruses by deaminating deoxycytidine (dC) into deoxyuridine (dU) in newly synthesized minus strand DNA, resulting in G-to-A hypermutation of the viral plus strand DNA. To clarify the mechanism of its function, we have examined the antiviral activity of APOBEC3G on human T-cell leukemia virus type 1 (HTLV-1), the first identified human retrovirus. Results: In this study, we have demonstrated that overexpressed as well as endogenous APOBEC3G were incorporated into HTLV-1 virions and that APOBEC3G inhibited the infection of HTLV-1. Interestingly, several inactive mutants of APOBEC3G also inhibited HTLV-1 and no G- to-A hypermutation was induced by APOBEC3G in HTLV-1 genome. Furthermore, we introduced the human immunodeficiency virus type 1 (HIV-1) vif gene into HTLV-1 producing cell line, MT-2, to antagonize APOBEC3G by reducing its intracellular expression and virion incorporation, which resulted in upregulation of the infectivity of produced viruses. Conclusion: APOBEC3G is incorporated into HTLV-1 virions and inhibits the infection of HTLV- 1 without exerting its cytidine deaminase activity. These results suggest that APOBEC3G might act on HTLV-1 through different mechanisms from that on HIV-1 and contribute to the unique features of HTLV-1 infection and transmission. to the Apobec superfamily of cytidine deaminases [5] andBackgroundAPOBEC3G, also known as CEM15 [1], is a host cellular inhibits the infectivity of these viruses by being packagedprotein which has a broad antiviral activity on a wide vari- into virions. During reverse transcription, it deaminatesety of retroviruses including HIV-1, other lentiviruses, and deoxycytidine (dC) into deoxyuridine (dU) in newly syn-murine leukemia virus (MLV) [2-4]. The protein belongs thesized minus strand DNA, resulting in either G-to-A Page 1 of 10 (page number not for citation purposes)Retrovirology 2005, 2:32 http://www.retrovirology.com ...