McGill University AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montréal, QC, Canada.
Retrovirology. 2011 Jul 1;8:52. doi: 10.1186/1742-4690-8-52.
Integration of the reverse transcribed viral genome into host chromatin is the hallmark of retroviral replication. Yet, during natural HIV infection, various unintegrated viral DNA forms exist in abundance. Though linear viral cDNA is the precursor to an integrated provirus, increasing evidence suggests that transcription and translation of unintegrated DNAs prior to integration may aid productive infection through the expression of early viral genes. Additionally, unintegrated DNA has the capacity to result in preintegration latency, or to be rescued and yield productive infection and so unintegrated DNA, in some circumstances, may be considered to be a viral reservoir. Recently, there has been interest in further defining the role and function of unintegrated viral DNAs, in part because the use of anti-HIV integrase inhibitors leads to an abundance of unintegrated DNA, but also because of the potential use of non-integrating lentiviral vectors in gene therapy and vaccines. There is now increased understanding that unintegrated viral DNA can either arise from, or be degraded through, interactions with host DNA repair enzymes that may represent a form of host antiviral defence. This review focuses on the role of unintegrated DNA in HIV infection and additionally considers the potential implications for antiviral therapy.
逆转录病毒基因组整合到宿主染色质中是逆转录病毒复制的标志。然而，在自然的 HIV 感染过程中，存在大量未整合的病毒 DNA 形式。虽然线性病毒 cDNA 是整合前病毒的前体，但越来越多的证据表明，在整合之前，未整合 DNA 的转录和翻译可能通过早期病毒基因的表达有助于有效的感染。此外，未整合的 DNA 有导致整合前潜伏的能力，或者被拯救并产生有效的感染，因此，在某些情况下，未整合的 DNA 可以被认为是病毒库。最近，人们对进一步定义未整合病毒 DNA 的作用和功能产生了兴趣，部分原因是抗 HIV 整合酶抑制剂的使用导致大量未整合的 DNA 产生，另一个原因是潜在的使用非整合慢病毒载体进行基因治疗和疫苗。现在越来越多的人了解到，未整合的病毒 DNA 可以通过与宿主 DNA 修复酶的相互作用而产生，也可以通过这些相互作用而被降解，这可能代表了一种宿主抗病毒防御的形式。本综述重点讨论了未整合 DNA 在 HIV 感染中的作用，并进一步考虑了其对抗病毒治疗的潜在影响。
