aInstitute of Microbiology, University Hospital of Lausanne, University of Lausanne, Lausanne bDepartment of Biosystems Science and Engineering, ETH Zurich cSwiss Institute of Bioinformatics, Basel, Switzerland.
Curr Opin HIV AIDS. 2015 Mar;10(2):90-5. doi: 10.1097/COH.0000000000000136.
HIV targets primary CD4(+) T cells. The virus depends on the physiological state of its target cells for efficient replication, and, in turn, viral infection perturbs the cellular state significantly. Identifying the virus-host interactions that drive these dynamic changes is important for a better understanding of viral pathogenesis and persistence. The present review focuses on experimental and computational approaches to study the dynamics of viral replication and latency.
It was recently shown that only a fraction of the inducible latently infected reservoirs are successfully induced upon stimulation in ex-vivo models while additional rounds of stimulation make allowance for reactivation of more latently infected cells. This highlights the potential role of treatment duration and timing as important factors for successful reactivation of latently infected cells. The dynamics of HIV productive infection and latency have been investigated using transcriptome and proteome data. The cellular activation state has shown to be a major determinant of viral reactivation success. Mathematical models of latency have been used to explore the dynamics of the latent viral reservoir decay.
Timing is an important component of biological interactions. Temporal analyses covering aspects of viral life cycle are essential for gathering a comprehensive picture of HIV interaction with the host cell and untangling the complexity of latency. Understanding the dynamic changes tipping the balance between success and failure of HIV particle production might be key to eradicate the viral reservoir.
目的综述：HIV 靶向初始 CD4(+)T 细胞。病毒依赖其靶细胞的生理状态来进行高效复制，而病毒感染则显著改变细胞状态。识别驱动这些动态变化的病毒-宿主相互作用，对于更好地理解病毒发病机制和持续性至关重要。本综述重点介绍了用于研究病毒复制和潜伏动力学的实验和计算方法。
最近发现：最近的研究表明，在体外模型中，只有一部分可诱导潜伏感染的储库在刺激下才能成功被诱导，而进一步的刺激则允许更多潜伏感染的细胞被重新激活。这突出了治疗持续时间和时机作为成功激活潜伏感染细胞的重要因素的潜在作用。利用转录组和蛋白质组数据研究了 HIV 复制和潜伏的动力学。细胞激活状态被证明是病毒重新激活成功的主要决定因素。潜伏模型已被用于探索潜伏病毒库衰减的动力学。
总结：时间是生物相互作用的一个重要组成部分。涵盖病毒生命周期各个方面的时间分析对于全面了解 HIV 与宿主细胞的相互作用以及理清潜伏的复杂性至关重要。了解导致 HIV 颗粒产生成功与失败之间平衡变化的动态变化可能是根除病毒库的关键。
