The goal is to develop an SIV/SHIV rhesus macaque model that more closely mimics HIV infections in humans than those models presently available. The most commonly used is SIV/SHIV in rhesus macaques of Indian origin. This model suffers from two limitations. First, there is a shortage of rhesus of Indian origin and secondly, the pathogenesis of SIV/SHIV in Indian rhesus does not closely mimic HIV infections in humans. SHIV/SIV models are either much more or much less pathogenic, when compared to HIV infections in humans. This project will focus on comparisons between rhesus macaques of Chinese and Indian origin. The investigators have statistically significant preliminary data that indicate that a new model in Chinese rhesus will be characterized by slowly progressing infections that more closely mimic HIV plasma virus loads in adult human infections. Viral load set points in SIV-infected Chinese rhesus were much closer to HIV set points than in all other animal models, including HIV in chimpanzees.
The Specific Aims are to: 1. compare SIV pathogenesis in vivo and in vitro using molecularly cloned SIVmac239 and uncloned SIVmac251 in rhesus of Chinese and Indian origin;
Specific Aim 2. compare the immunopathogenesis in mucosal and peripheral tissues of SIV-infected Chinese and Indian rhesus macaques throughout the course of infection;
and Specific Aim 3. test the pathogenesis of SIVmac in rhesus macaques that were caught in the wild in southern China. The investigators seek to develop a more slowly progressing model that will offer better predictive data for human AIDS.
| Ling, Binhua; Veazey, Ronald S; Hart, Mike et al. (2007) Early restoration of mucosal CD4 memory CCR5 T cells in the gut of SIV-infected rhesus predicts long term non-progression. AIDS 21:2377-85 |
