%0 Journal Article
%T Viral complementation allows HIV-1 replication without integration
%A Huub C Gelderblom
%A Dimitrios N Vatakis
%A Sean A Burke
%A Steven D Lawrie
%A Gregory C Bristol
%A David N Levy
%J Retrovirology
%D 2008
%I BioMed Central
%R 10.1186/1742-4690-5-60
%X We employed reporter viruses and quantitative real time PCR to examine gene expression and virus replication during coinfection with integrating and non-integrating HIV-1. Most cells which contained only uDNA displayed no detected expression from fluorescent reporter genes inserted into early (Rev-independent) and late (Rev-dependent) locations in the HIV-1 genome. Coinfection with an integrated provirus resulted in a several fold increase in the number of cells displaying uDNA early gene expression and efficiently drove uDNA into late gene expression. We found that coinfection generates virions which package and deliver uDNA-derived genomes into cells; in this way uDNA completes its replication cycle by viral complementation. uDNA-derived genomes undergo recombination with the integrated provirus-derived genomes during second round infection.This novel mode of retroviral replication allows survival of viruses which would otherwise be lost because of a failure to integrate, amplifies the effective amount of cellular coinfection, increases the replicating HIV-1 gene pool, and enhances the opportunity for diversification through errors of polymerization and recombination.Integration of the retroviral cDNA into cellular chromatin is a basic feature of retroviral replication [1-3] and is mediated by the viral integrase enzyme, a product of the pol gene whose substrate is a linear form of viral DNA. Chromatin supports the high levels of gene expression necessary for production of new virions and completion of the viral life cycle. Integration also ensures that the viral genome will persist for the life of the cell. When viral latency follows integration, one consequence is viral persistence in the face of highly suppressive antiviral therapy [4,5]. The integration process provides a target for the development of antiviral drugs [6].When integration fails, virus replication is thought to be irretrievably lost, since unintegrated DNA (uDNA) by itself evidently does not sup
%U http://www.retrovirology.com/content/5/1/60