Abstract
Accumulation of high levels of unintegrated viral DNA is a common feature of retroviral infection. It was recently discovered that coinfection of cells with integrated and unintegrated HIV-1 can result in complementation, allowing viral replication in the absence of integration. This new mode of HIV-1 replication has numerous implications for the function of unintegrated viral DNA and its application as a therapeutic vector.
Highlights
With retroviruses such as HIV, life seems to be simple and straightforward
The RNA genome transcribed from the unintegrated DNA can be packaged into the virion and is able to effectively compete with the wild-type genome for packaging. These results clearly suggest that the unintegrated DNA molecules have the full potential in this regard of any HIV DNA
MFiogduerleo1f complementation between unintegrated and integrated HIV-1 Model of complementation between unintegrated and integrated HIV-1. (A) Viral transcription in the absence of integration generates all classes of viral transcripts, but only early proteins such as Tat, Rev, and Nef are synthesized at low levels
Summary
With retroviruses such as HIV, life seems to be simple and straightforward. As a single infectious particle, the virus converts its RNA genome into DNA and incorporates it into the host genome. Their limitations in expressing viral genes appear to be only temporary, imposed by the lack of sufficient Tat and Rev function With this understanding of their full potential, the question of whether these unintegrated DNA molecules deserve a second chance becomes obvious. The authors confirmed that in the presence of the second virus, the unintegrated HIV DNA molecules were driven to express both early and late genes, as well as viral genomes that were subsequently packaged and released from the cell. They started on a new journey that gave them a second opportunity to integrate. This complementation between the few integrated and the majority unintegrated would prevent possible losses of viral genetic diversity
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