%0 Journal Article
%T The second chance story of HIV-1 DNA: Unintegrated? Not a problem!
%A Yuntao Wu
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-61
%X 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 then incorporates it into the host genome. Once this happens, the rest of the viral life cycle is largely a happy free ride from the host. However, for the viral population as a whole, the truth is that only a very small proportion of the viruses have such a productive life. The vast majority of the viral DNA remains isolated from the host chromatin [1-8]. These DNA molecules are euphemistically referred to as the "unintegrated"; in reality, they are the "left behind" and down regulated (gene expression is low and restricted to only early genes [9-11]). The stakes are high; they are at risk of being destroyed and cleared [12,13]. We still do not understand why most HIV DNA cannot or does not integrate, and other questions remain as well: is there something wrong with these "unintegrated," and do they deserve a second chance?Answering these questions is not as simple as it seems. First, within a viral population, we do not know which viral DNA is destined to integrate, and there is no marker to differentiate this phenotype. Second, against a background of viral activities from both the integrated and the unintegrated, it is difficult to monitor and track viral behavior from the unintegrated alone. In spite of these hurdles, in the recent article by Gelderblom and co-authors [14], these questions were elegantly addressed using a very creative approach. The authors employed coinfection of cells with the wild-type virus and an integrase mutant, both of which were labelled with different fluorescent reporters. This permitted tracking and delicate differentiation of the wild-type and the unintegrated viruses.To address the question of whether the unintegrated viral DNA remains functional, the authors used an integrase inhibitor and an integrase mutant virus, D116N [15]. They also tagged the viral early genes with green
%U http://www.retrovirology.com/content/5/1/61