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Modeling the evolution of SIV sooty mangabey progenitor virus towards HIV-2 using humanized mice
Virology ( IF 3.7 ) Pub Date : 2017-07-24 , DOI: 10.1016/j.virol.2017.07.005
Kimberly Schmitt , Dipu Mohan Kumar , James Curlin , Leila Remling-Mulder , Mark Stenglein , Shelby O’Connor , Preston Marx , Ramesh Akkina

HIV-2 is thought to have originated from an SIV progenitor native to sooty mangabeys. To model the initial human transmission and understand the sequential viral evolution, humanized mice were infected with SIVsm and serially passaged for five generations. Productive infection was seen by week 3 during the initial challenge followed by chronic viremia and gradual CD4+ T cell decline. Viral loads increased by the 5th generation resulting in more rapid CD4+ T cell decline. Genetic analysis revealed several amino acid substitutions that were nonsynonymous and fixed in multiple hu-mice across each of the 5 generations in the nef, env and rev regions. The highest rate of substitution occurred in the nef and env regions and most were observed within the first two generations. These data demonstrated the utility of hu-mice in modeling the SIVsm transmission to the human and to evaluate its potential sequential evolution into a human pathogen of HIV-2 lineage.



中文翻译:

使用人源化小鼠模拟SIV煤烟型黑猩猩祖细胞病毒向HIV-2的进化

人们认为,HIV-2起源于黑社会性黑猩猩的SIV祖先。为了模拟最初的人类传播并了解病毒的顺序进化,将人源化小鼠感染了SIVsm,并连续传代了五代。在最初攻击的第3周时发现生产性感染,随后是慢性病毒血症和CD4 + T细胞逐渐下降。第五代病毒载量增加,导致CD4 + T细胞下降更快。遗传分析显示,在nef,envrev地区的5代中的每一个中,多个氨基酸替代都是不同义的,并固定在多个hu-小鼠中。最高的取代率发生在nefenv区域,大多数在前两代内观察到。这些数据证明了在模拟SIVsm向人的传播以及评估其向HIV-2谱系的人类病原体的潜在进化过程中,小鼠具有实用性。

更新日期:2017-07-24
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