APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation - Comparisons with APOBEC3G
APOBEC3F can inhibit the accumulation of HIV-1 reverse transcription products in the absence of hypermutation - Comparisons with APOBEC3G
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DOI：
10.1074/jbc.m607298200
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发表时间：
2007-01-26
影响因子：
4.8
通讯作者：
Malim, Michael H.
中科院分区：
文献类型：
--
作者：
Holmes, Rebecca K.;Koning, Fransje A.;Malim, Michael H.
APOBEC3F(载脂蛋白B mRNA编辑酶催化多肽1样蛋白3F)是一种胞苷脱氨酶，与APOBEC3G一样，能够限制HIV-1/Delta vif的复制。初步研究显示，在这些蛋白质存在的情况下，病毒的cdna发生了大量的突变，这表明胞苷脱氨作用支持了对感染的抑制。然而，我们最近发现，通过C端胞苷脱氨酶基序突变而产生的无催化活性的APOBEC3G蛋白仍然具有显著的抗病毒作用。在这里，我们已经产生了一组APOBEC3F突变蛋白，并表明C端胞苷脱氨酶基序是催化活性所必需的，而催化活性对于APOBEC3F的抗病毒作用并不是必需的。此外，我们证明了野生型和催化失活的APOBEC3F和APOBEC3G蛋白的抗病毒活性与病毒反转录产物积累的减少很好地对应。APOBEC3F和APOBEC3G之间的进一步比较表明，脱氨酶活性的丧失对APOBEC3G功能的损害比对APOBEC3F功能的损害更大，这反映在对反向转录积累抑制和抗病毒活性的干扰上。综上所述，这些数据表明，在没有胞苷脱氨基的情况下，APOBEC3F和APOBEC3G都能够作为抗病毒因子发挥作用，这种编辑无关的活性是APOBEC蛋白介导的抗病毒表型的一个重要方面，但APOBEC3F可能是一个更好的研究模型。
APOBEC3F (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1-like protein 3F) is a cytidine deaminase that, like APOBEC3G, is able to restrict the replication of HIV-1/Delta vif. Initial studies revealed high numbers of mutations in the cDNA of viruses produced in the presence of these proteins, suggesting that cytidine deamination underpinned the inhibition of infection. However, we have recently shown that catalytically inactive APOBEC3G proteins, derived through mutation of the C-terminal cytidine deaminase motif, still exert a substantial antiviral effect. Here, we have generated a panel of APOBEC3F mutant proteins and show that the C-terminal cytidine deaminase motif is essential for catalytic activity and that catalytic activity is not necessary for the antiviral effect of APOBEC3F. Furthermore, we demonstrate that the antiviral activities of wild-type and catalytically inactive APOBEC3F and APOBEC3G proteins correspond well with reductions in the accumulation of viral reverse transcription products. Additional comparisons between APOBEC3F and APOBEC3G suggest that the loss of deaminase activity is more detrimental to APOBEC3G function than to APOBEC3F function, as reflected by perturbations to the suppression of reverse transcript accumulation as well as antiviral activity. Taken together, these data suggest that both APOBEC3F and APOBEC3G are able to function as antiviral factors in the absence of cytidine deamination, that this editing-independent activity is an important aspect of APOBEC protein-mediated antiviral phenotypes, but that APOBEC3F may be a better model in which to study it.