Induction of AIDS in rhesus monkeys by a recombinant simian immunodeficiency virus expressing nef of human immunodeficiency virus type 1
Induction of AIDS in rhesus monkeys by a recombinant simian immunodeficiency virus expressing nef of human immunodeficiency virus type 1
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DOI：
10.1128/jvi.73.7.5814-5825.1999
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发表时间：
1999-07-01
影响因子：
5.4
通讯作者：
Desrosiers, RC
中科院分区：
文献类型：
--
作者：
Alexander, L;Du, ZJ;Desrosiers, RC
nef基因存在于所有灵长类慢病毒中，包括人类免疫缺陷病毒1型（HIV-1）和猕猴免疫缺陷病毒（SIVmac）。然而，HIV-1和SIVmac的nef基因表现出最小的序列同一性，并且并非所有特性都由两者共享。SIVmac 239的nef序列在最佳表达的情况下被HIV-1的四个独立nef等位基因所取代。HIV-1 nef序列的来源包括NL 4-3、来源于重组感染的恒河猴的变体NL 4 -3基因、患者nef等位基因和nef共有序列;在感染这些SHIVnef嵌合体的16只恒河猴中，9只在长时间内保持高病毒载量，如用亲本SIVmac 239观察到的，6只在感染后52至110周死于AIDS。在表达这些独立的HIV-1 nef等位基因的四种不同SIV重组体中观察到持续的高蟾蜍频率。用其他重组SHIVnef构建体感染导致感染猴中的序列变化，其产生开放的nef阅读框架或优化HIV-1 nef翻译背景。HIV-1 nef基因在所有SHIV nef感染的猴子中一致保留。这些结果表明，HIV-1 nef可以替代SIVmac nef在体内产生致病性感染。然而，该模型不能在100%的感染动物中持续获得高病毒载量，如用亲本SIVmac 239观察到的。
A nef gene is present in all primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus of macaque monkeys (SIVmac). However, the nef genes of HIV-1 and SIVmac exhibit minimal sequence identity, and not all properties are shared by the two. Nef sequences of SIVmac239 were replaced by four independent nef alleles of HIV-1 in a context that was optimal For expression, The sources of the HIV-1 nef sequences included NL 4-3, a variant NL 4-3 gene derived from a recombinant-infected rhesus monkey, a patient nef allele, and a nef consensus sequence; Of 16 rhesus monkeys infected with these SHIVnef chimeras, 9 maintained high viral loads for prolonged periods, as observed with the parental SIVmac239, and 6 have died with AIDS 52 to 110 weeks postinfection, Persistent high toads were observed at similar frequencies with the four different SIV recombinants that expressed these independent HIV-1 nef alleles, Infection with other recombinant SHIVnef constructions resulted in sequence changes in infected monkeys that either created an open nef reading frame or optimized the HIV-1 nef translational context. The HIV-1 nef gene was uniformly retained in all SHIV nef-infected monkeys. These results demonstrate that HIV-1 nef can substitute for SIVmac nef in vivo to produce a pathogenic infection. However, the model suffers from an inability to consistently obtain persisting high viral loads in 100% of the infected animals, as is observed with the parental SIVmac239.