NATURAL HISTORY OF SIVMAC BK28 & H824 INFECTION IN MACACA NEMESTRINA

在这个项目中，我们试图确定疾病进展的早期预测M。通过使用两种密切相关的SIV攻击菌株，在M.穆拉塔 这些分子克隆的使用提供了独特的机会，在使用分子定义的病毒的同时模拟艾滋病的快速和缓慢进展。 正在进行病毒和免疫鉴定。 四只动物感染SIVmacH824或BK 28。 至少每月进行一次病毒载量测量，确定H824是恒河猴中致病性更强的病毒，其产生的病毒载量在第20周始终比BK 28产生的病毒载量高1 - 2个对数。 感染H824的一只动物在感染后19周被安乐死。 其余3只动物的病毒载量（不考虑接种物）下降至不可检测水平。尽管病毒载量下降，但剩余的H824感染动物在感染后40周发展为AIDS，并在58周时因AIDS样症状而被安乐死。 这两只BK28感染的动物继续茁壮成长，尽管它们确实表现出CD4下降。 在第16周内对产生IFN β的细胞进行计数;结果表明IFN β阳性CD4+和CD8+细胞的诱导，尽管在感染不同克隆的动物之间没有显著差异。 有趣的是，IFN β产生细胞的峰值数量与峰值病毒载量同步发生。 我们在整个感染过程中继续进行这些测定，并结合其他细胞因子和活化标志物，以更好地检查细胞因子反应。 我们检测了RANTES的血浆水平，发现尽管病毒载量下降，但在BK 28感染的动物中表达仍得以维持。 在一只存活58周的H824感染动物中，RANTES水平随着病毒载量的下降而下降。 这些结果有力地支持了M.涅梅斯特里纳。 未来的项目将结合本研究中获得的信息，为SIV和HIV引起的疾病开发有效的治疗方法。

In this project we seek to identify early predictors of disease progression in M. nemestrina through the use of two closely related SIV challenge strains that differ markedly in their pathogenicity as determined in M. mulatta. The use of these molecular clones affords the unique opportunity to model fast and slow progression to AIDS while using molecularly defined viruses. Both viral and immune characterizations are being performed. Four animals were infected with either SIVmacH824 or BK28. Viral load measurements were taken at least monthly and H824, determined to be the more pathogenic virus in rhesus macaques, produced a viral load that was consistently 1-2 logs higher than the viral load produced by BK28 through week 20. One animal infected with H824 was euthanized at 19 weeks postinfection. The viral loads in the three remaining animals, regardless of inoculum, declined to undetectable levels. Despite this decline in viral load, the remaining H824-infected animal progressed to AIDS at 40 weeks postinfection and was euthanized at 58 weeks due to AIDS-like symptoms. The two BK28-infected animals continue to thrive although they do demonstrate CD4 decline. Enumeration of cytokine-producing cells was performed through week 16; the results demonstrated the induction of IFN(-positive CD4+ and CD8+ cells, although there were no significant differences between animals infected with different clones. Interestingly, peak numbers of IFN(-producing cells occurred synchronously with peak viral load. We are continuing these assays throughout the course of infection and are incorporating additional cytokine and activation markers to better examine the cytokine response. We examined plasma levels of RANTES and found that expression was maintained in BK28-infected animals despite decline of viral load. RANTES levels dropped subsequent to the drop in viral load in the one H824-infected animal that survived 58 weeks. These results strongly support the hypothesis that there would be a differential pathogenesis in M. nemestrina. Future projects will incorporate information obtained in this study to develop effective therapies for SIV- and HIV-induced disease.