Abstract
BackgroundApolipoprotein 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.ResultsIn 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.ConclusionAPOBEC3G 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.
Highlights
Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is a host cellular protein with a broad antiviral activity
These results suggest that APOBEC3G might act on human T-cell leukemia virus type 1 (HTLV-1) through different mechanisms from that on human immunodeficiency virus type 1 (HIV-1) and contribute to the unique features of HTLV-1 infection and transmission
Since we detected the incorporation of overexpressed APOBEC3G into HTLV-1 virions, we examined the incorporation of endogenous APOBEC3G into HTLV-1 virions using an HTLV-1 producing cell line, MT2, which expressed endogenous APOBEC3G (Fig. 1D, lane 1, upper panel)
Summary
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. The protein belongs to the Apobec superfamily of cytidine deaminases [5] and inhibits the infectivity of these viruses by being packaged into virions During reverse transcription, it deaminates deoxycytidine (dC) into deoxyuridine (dU) in newly synthesized minus strand DNA, resulting in either G-to-A (page number not for citation purposes). This suggests that APOBEC3G has a broad antiviral activity on retroviruses and on other viruses through different mechanisms from that on retroviruses
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