Johns Hopkins University School of Medicine and Howard Hughes Medical Institute, Baltimore, MD 22105, USA.
Curr Opin HIV AIDS. 2013 Jul;8(4):318-25. doi: 10.1097/COH.0b013e328361eaca.
Recent developments have generated renewed interest in the possibility of curing HIV-1 infection. This review describes some of the practical challenges that will need to be overcome if curative strategies are to be successful.
The latent reservoir for HIV-1 in resting memory CD4 T cells is the major barrier to curing the infection. The most widely discussed approach to curing the infection involves finding agents that reverse latency in resting CD4 T cells, with the assumption that the cells will then die from viral cytopathic effects or be lysed by host cytolytic T lymphocytes (CTLs). A major challenge is the development of in-vitro models that can be used to explore mechanisms and identify latency-reversing agents (LRAs). Although several models have been developed, including primary cell models, none of them may fully capture the quiescent state of the cells that harbour latent HIV-1 in vivo. An additional problem is that LRAs that do not cause T-cell activation may not lead to the death of infected cells. Finally, measuring the effects of LRAs in vivo is complicated by the lack of correlation between different assays for the latent reservoir.
Progress on these practical issues is essential to finding a cure.
最近的发展激发了人们对治愈 HIV-1 感染的可能性的新兴趣。本文描述了治愈策略如果要成功，就需要克服的一些实际挑战。
HIV-1 在静止记忆 CD4 T 细胞中的潜伏库是治愈感染的主要障碍。治愈感染最广泛讨论的方法涉及寻找逆转静止 CD4 T 细胞潜伏期的药物，假设这些细胞随后会因病毒细胞病变效应而死亡，或被宿主细胞毒性 T 淋巴细胞 (CTL) 溶解。一个主要的挑战是开发可以用于探索机制和识别潜伏逆转剂 (LRA) 的体外模型。尽管已经开发了几种模型，包括原代细胞模型，但它们都可能无法完全捕捉到体内携带潜伏 HIV-1 的细胞的静止状态。另一个问题是，不会引起 T 细胞活化的 LRA 可能不会导致感染细胞死亡。最后，由于缺乏潜伏库的不同检测方法之间的相关性，体内测量 LRA 的效果很复杂。
在这些实际问题上取得进展对于寻找治愈方法至关重要。
