Kar Sujata, Cummings Phoebe, Alexander Louis
Department of Epidemiology and Public Health, Yale University School of Medicine, 60 College Street, New Haven, CT 06520, USA.
J Gen Virol. 2003 Dec;84(Pt 12):3227-3231. doi: 10.1099/vir.0.19449-0.
Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) Vif share limited homology and display species-specific activity, leading to speculation that Vif sequences could determine the block in HIV-1 replication in rhesus monkeys. To address this issue, we engineered a novel SIV recombinant in which HIV-1 vif replaced SIV vif in a SIVmac239 background. Insertion of HIV-1 vif into the SIV vif locus did not produce a replication-competent virus. Therefore, we inserted HIV-1 vif sequences into the SIV nef locus, which produced a recombinant that, in the absence of SIV vif sequences, replicated similarly to wild-type SIVmac239 in rhesus monkey PBMC. From these studies we conclude that the HIV-1 replication block in rhesus monkeys is almost certainly not Vif determined. These studies also suggest that SHIV/NVif or derivative sequences could be utilized for structure/function studies of HIV-1 Vif in experimentally infected rhesus monkeys.
1型人类免疫缺陷病毒（HIV-1）和猴免疫缺陷病毒（SIV）的病毒感染因子（Vif）具有有限的同源性，并表现出物种特异性活性，这引发了人们的猜测，即Vif序列可能决定了HIV-1在恒河猴体内复制的障碍。为了解决这个问题，我们构建了一种新型的SIV重组体，其中在SIVmac239背景下，HIV-1的vif取代了SIV的vif。将HIV-1的vif插入SIV的vif基因座并未产生具有复制能力的病毒。因此，我们将HIV-1的vif序列插入SIV的nef基因座，产生了一种重组体，在没有SIV的vif序列的情况下，该重组体在恒河猴外周血单个核细胞（PBMC）中的复制情况与野生型SIVmac239相似。从这些研究中我们得出结论，恒河猴体内HIV-1复制的障碍几乎肯定不是由Vif决定的。这些研究还表明，SHIV/NVif或其衍生序列可用于在实验感染的恒河猴中对HIV-1的Vif进行结构/功能研究。
