Yu Qin, Chen Darlene, König Renate, Mariani Roberto, Unutmaz Derya, Landau Nathaniel R
Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
J Biol Chem. 2004 Dec 17;279(51):53379-86. doi: 10.1074/jbc.M408802200. Epub 2004 Oct 4.
In the human genome the apolipoprotein B mRNA-editing enzyme catalytic polypeptide (APOBEC)3 gene has expanded into a tandem array of genes termed APOBEC3A-G. Two members of this family, APOBEC3G and APOBEC3F, have been found to have potent activity against virion infectivity factor deficient (Deltavif) human immunodeficiency virus 1 (HIV-1). These enzymes become encapsidated in Deltavif HIV-1 virions and in the next round of infection deaminate the newly synthesized reverse transcripts. The lentiviral Vif protein prevents the deamination by inducing the degradation of APOBEC3G and APOBEC3F. We report here that two additional APOBEC3 family members, APOBEC3B and APOBEC3C, have potent antiviral activity against simian immuno-deficiency virus (SIV), but not HIV-1. Both enzymes were encapsidated in HIV-1 and SIV virions and were active against Deltavif SIV(mac) and SIV(agm). SIV Vif neutralized the antiviral activity of APOBEC3C, but not that of APOBEC3B. APOBEC3B induced abundant G --> A mutations in both wild-type and Deltavif SIV reverse transcripts. APOBEC3C induced substantially fewer mutations. APOBEC3F was found to be active against SIV and sensitive to SIV(mac) Vif. These findings raise the possibility that the different APOBEC3 family members function to neutralize specific lentiviruses.
在人类基因组中，载脂蛋白B信使核糖核酸编辑酶催化多肽（APOBEC）3基因已扩展为一个串联排列的基因阵列，称为APOBEC3A - G。已发现该家族的两个成员，APOBEC3G和APOBEC3F，对病毒体感染因子缺陷型（Deltavif）人类免疫缺陷病毒1型（HIV - 1）具有强大活性。这些酶被包裹在Deltavif HIV - 1病毒体中，并在下一轮感染中使新合成的逆转录产物发生脱氨基作用。慢病毒Vif蛋白通过诱导APOBEC3G和APOBEC3F的降解来阻止脱氨基作用。我们在此报告，另外两个APOBEC3家族成员，APOBEC3B和APOBEC3C，对猿猴免疫缺陷病毒（SIV）具有强大的抗病毒活性，但对HIV - 1没有活性。这两种酶都被包裹在HIV - 1和SIV病毒体中，并且对Deltavif SIV（mac）和SIV（agm）具有活性。SIV Vif中和了APOBEC3C的抗病毒活性，但没有中和APOBEC3B的抗病毒活性。APOBEC3B在野生型和Deltavif SIV逆转录产物中均诱导了大量的G→A突变。APOBEC3C诱导的突变明显较少。发现APOBEC3F对SIV有活性且对SIV（mac）Vif敏感。这些发现增加了不同APOBEC3家族成员发挥作用以中和特定慢病毒的可能性。
