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转移/创始人人猿人免疫缺陷病毒的适应,用于在 rhesus macaques 中增强复制

Anya Bauer¹, Emily Lindemuth¹, Francesco Elia Marino¹

¹Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

|July 3, 2023

概括

研究人员开发了一种新的猿人免疫缺陷病毒 (SHIV) 模型,SHIV.C.CH505.v2,用于改善的HIV-1研究. 这种增强的病毒模型显示出更好的复制和持久性,有助于研究艾滋病毒的传播,病变和治愈.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
灵长类动物模型

背景情况:

传染/创始人 (TF) 猿人免疫缺陷病毒 (SHIV) 对非人类灵长类动物的HIV-1研究至关重要.
SHIV.C.CH505,一种TF SHIV,模拟了HIV-1 Env生物学的关键,但与人类感染相比,的病毒载量变化和较低.
在不影响Env生物学的情况下提高SHIV适应性对于更强大的临床前研究至关重要.

研究的目的:

识别和生成一个适应的SHIV.C.CH505与改善的复制适应性在 rhesus macaques.
在适应的病毒中保持真实的HIV-1 Env生物学和中和化配置文件.
为非人类灵长类动物 (NHP) 研究HIV-1传播,病原和治愈创建一种优越的病毒试剂.

主要方法:

对感染SHIV.C.CH505的进行了序列分析,以确定与较高病毒血量相关的突变.
在体内突变选择和竞争试验中,分离出一种适应最小的SHIV,具有五种氨基酸的变化.
在体外和体内验证适应的SHIV的性能,包括进入,复制和与父病毒竞争.
通过抗逆转录病毒疗法评估病毒持久性,并在治疗中断后恢复.

主要成果:

产生了适应最小的SHIV.C.CH505.v2,具有五种特定氨基酸突变.
适应病毒在中显著提高了复制能力,以增长优势超越了父母的SHIV.
SHIV.C.CH505.v2 保持了 CCR5 热带性,二级中和性,以及真正的 Env 特性.
适应病毒在抑制性抗逆转录病毒疗法中持续存在,并在中断后复苏,模仿艾滋病毒感染的方面.

结论:

SHIV.C.CH505.v2代表了一种具有良好的特征,最小适应的病毒试剂,具有增强的复制能力.
这种改进的SHIV模型保留了原生Env属性,使其对NHP研究有价值.
增强的病毒使得在临床前环境中更准确地建模HIV-1传播,病变和治疗干预措施.

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