Long-Term Restriction by APOBEC3F Selects Human Immunodeficiency Virus Type 1 Variants with Restored Vif Function
Long-Term Restriction by APOBEC3F Selects Human Immunodeficiency Virus Type 1 Variants with Restored Vif Function
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DOI：
10.1128/jvi.00632-10
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发表时间：
2010-10-01
影响因子：
5.4
通讯作者：
Harris, Reuben S.
中科院分区：
文献类型：
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作者：
Albin, John S.;Hache, Guylaine;Harris, Reuben S.
人免疫缺陷病毒1型（HIV-1）vif中的串联终止突变K26 X和H27 X损害稳定表达APOBEC 3F（A3 F）或APOBEC 3G（A3 G）的人T细胞系中的病毒复制。我们以前报道，部分耐A3 G可以在这些VIF缺陷病毒通过核苷酸A200到T/C颠换和vpr无效突变，但这些分离株仍然容易受到A3 F的限制。在这里，进行了长期选择实验，以确定这些A3 G选择的分离株如何在A3 F存在下进化传播。我们发现，A3 F和A3 G一样，能够进行有效的长期限制，最终选择可遗传的抗性。在所有7种情况下，选择的分离株恢复了Vif功能以科普A3 F活性。在两个分离株Vif Q26-Q27和Y26-Q27中，抗性表型在分子克隆中重现，但当在其他野生型病毒背景的背景下分析所选vif等位基因时，出现了不同的结果。尽管具有Vif Q26-Q27或Y26-Q27的HIV-1克隆完全能够克服A3 F，但它们现在对A3 G的限制敏感。与先前的研究一致，26位的赖氨酸被证明是A3 G中和所必需的。这些数据联合收割机表明A3 F和A3 G至少部分地施加不同的选择压力，并且Vif功能可能是在A3 F存在下病毒复制所必需的。
Tandem stop mutations K26X and H27X in human immunodeficiency virus type 1 (HIV-1) vif compromise virus replication in human T-cell lines that stably express APOBEC3F (A3F) or APOBEC3G (A3G). We previously reported that partial resistance to A3G could develop in these Vif-deficient viruses through a nucleotide A200-to-T/C transversion and a vpr null mutation, but these isolates were still susceptible to restriction by A3F. Here, long-term selection experiments were done to determine how these A3G-selected isolates might evolve to spread in the presence of A3F. We found that A3F, like A3G, is capable of potent, long-term restriction that eventually selects for heritable resistance. In all 7 instances, the selected isolates had restored Vif function to cope with A3F activity. In two isolates, Vif Q26-Q27 and Y26-Q27, the resistance phenotype recapitulated in molecular clones, but when the selected vif alleles were analyzed in the context of an otherwise wild-type viral background, a different outcome emerged. Although HIV-1 clones with Vif Q26-Q27 or Y26-Q27 were fully capable of overcoming A3F, they were now susceptible to restriction by A3G. Concordant with prior studies, a lysine at position 26 proved essential for A3G neutralization. These data combine to indicate that A3F and A3G exert at least partly distinct selective pressures and that Vif function may be essential for the virus to replicate in the presence of A3F.