Abstract:
By acclimatizing CCR5-tropic tier 1B SHIV-MK1 to rhesus monkeys, a tier 2 SHIV-MK38 strain with neutralization resistance and high replication ability was generated. In this study, we generated SHIV-MK38C, a monkey-infectious consensus molecular clone of SHIV-MK38. Analysis using pseudotype viruses showed that MK38C was tier 1C because it lacked the N169D mutation, which is the most important mutation for neutralization resistance. MK38C harboring the N169D mutation became tier 2. However, the replication ability of SHIV-MK38C with N169D was low; more than 17 weeks elapsed before its detection in monkeys. Tier 1C MK38C was sensitive to a CD4 mimic. Therefore, SHIV-MK38C could be used to evaluate CD4 mimics in vivo.
摘要:
通过使CCR5热带1BSHIV-MK1适应恒河猴,产生了具有中和抗性和高复制能力的二级SHIV-MK38菌株。在这项研究中,我们产生了SHIV-MK38C,SHIV-MK38的猴子感染的共有分子克隆。使用假型病毒的分析表明,MK38C是1C级,因为它缺乏N169D突变,这是中和抗性最重要的突变。携带N169D突变的MK38C成为第2层。然而,SHIV-MK38C与N169D的复制能力较低;在猴子中检测到它之前已经过去了17周以上。Tier1CMK38C对CD4模拟物敏感。因此,SHIV-MK38C可用于评估体内CD4模拟物。