Selection of Unadapted, Pathogenic SHIVs Encoding Newly Transmitted HIV-1 Envelope Proteins
Selection of Unadapted, Pathogenic SHIVs Encoding Newly Transmitted HIV-1 Envelope Proteins
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DOI：
10.1016/j.chom.2014.08.003
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发表时间：
2014-09-10
影响因子：
30.3
通讯作者：
Hatziioannou, Theodora
中科院分区：
文献类型：
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作者：
Del Prete, Gregory Q.;Ailers, Braiden;Hatziioannou, Theodora
用基于SIVMAC但表达HIV-1包膜（Env）糖蛋白（SHIV）的嵌合病毒感染猕猴仍然是评估艾滋病预防和治疗策略的最有力模型。不幸的是，目前只有少数SHIV可用。此外，它们的产生需要对猕猴中的HIV-1 Env序列进行广泛的适应，因此它们可能无法准确地代表人类中循环的HIV-1 Env蛋白，这可能限制了它们的翻译实用性。我们开发了一种从新传播的HIV-1毒株中产生大量表达Env蛋白的SHIV构建体的策略。通过用多种SHIV变体的混合物感染恒河猴，我们选择了可以在免疫完整的恒河猴中复制并引起艾滋病样疾病的SHIV，而不需要动物间的传代。其中一种SHIV可以通过粘膜传播。我们证明了通过这种方法产生的SHIV用于评估中和抗体施用作为对粘膜SHIV攻击的保护的效用。
Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.