APOBEC3G targets human T-cell leukemia virus type 1.
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.


CONCLUSIONS
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.
Sasada
Amane
A
Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawaracho, Sakyo-ku, Kyoto 606-8507, Japan. amasasa@kuhp.kyoto-u.ac.jp
Takaori-Kondo
Akifumi
A
Shirakawa
Kotaro
K
Kobayashi
Masayuki
M
Abudu
Aierkin
A
Hishizawa
Masakatsu
M
Imada
Kazunori
K
Tanaka
Yuetsu
Y
Uchiyama
Takashi
T
D000071480:APOBEC-3G Deaminase; D002460:Cell Line; D003564:Cytidine Deaminase; D016346:Gene Products, vif / Q000378:metabolism; D015497:HIV-1 / Q000502:physiology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009700:Nucleoside Deaminases / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000378:metabolism; D014779:Virus Replication; D054320:vif Gene Products, Human Immunodeficiency Virus
D016346:Gene Products, vif; D012097:Repressor Proteins; D054320:vif Gene Products, Human Immunodeficiency Virus; D009700:Nucleoside Deaminases; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase