Choudhary Shailesh K, Rezk Naser L, Ince William L, Cheema Manzoor, Zhang Liguo, Su Lishan, Swanstrom Ronald, Kashuba Angela D M, Margolis David M
Department of Medicine, University of North Carolina, Chapel Hill, 27599, USA.
J Virol. 2009 Aug;83(16):8254-8. doi: 10.1128/JVI.00580-09. Epub 2009 Jun 3.
A small animal model that reproduces human immunodeficiency virus type 1 (HIV-1) pathogenesis may allow modeling of new therapeutic strategies in ways not approachable in mononuclear cell culture. We find that, as in humans, combination antiretroviral therapy (ART) in humanized (hu-) Rag2(-/-)gamma(c)(-/-) mice allows suppression of viremia below the limits of detection and recovery of CD4(+) cells, while interruption of ART results in viral rebound and renewed loss of CD4(+) T cells. Failure of ART in infected mice is associated with the appearance of drug resistance mutations. The hu-Rag2(-/-)gamma(c)(-/-) mouse may therefore facilitate testing of novel approaches to HIV replication and persistence.
一种能够重现人类免疫缺陷病毒1型(HIV-1)发病机制的小动物模型,或许可以通过单核细胞培养无法实现的方式对新的治疗策略进行建模。我们发现,与人类情况一样,在人源化(hu-)Rag2(-/-)γc(-/-)小鼠中采用联合抗逆转录病毒疗法(ART)可将病毒血症抑制到检测限以下,并使CD4(+)细胞恢复,而中断ART则会导致病毒反弹以及CD4(+)T细胞再次减少。感染小鼠中ART治疗失败与耐药性突变的出现有关。因此,hu-Rag2(-/-)γc(-/-)小鼠可能有助于测试针对HIV复制和持续存在的新方法。