Stable multi-infection of splenocytes during SIV infection - the basis for continuous recombination
1 Department of Virology, Saarland University, Homburg D-66421, Germany
2 Department of Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria
3 Unit of Infection Models, German Primate Center, Göttingen D-37077, Germany
4 ICREA Infection Biology Laboratory, Department of Experimental and Health Sciences, University Pompeu Fabra, Barcelona 08003, Spain
Retrovirology 2012, 9:31 doi:10.1186/1742-4690-9-31Published: 23 April 2012
Recombination is an important mechanism in the generation of genetic diversity of the human (HIV) and simian (SIV) immunodeficiency viruses. It requires the co-packaging of divergent RNA genomes into the same retroviral capsid and subsequent template switching during the reverse transcription reaction. By HIV-specific fluorescence in situ hybridization (FISH), we have previously shown that the splenocytes from 2 chronically infected patients with Castelman's disease were multi-infected and thus fulfill the in vivo requirements to generate genetic diversity by recombination. In order to analyze when multi-infection first occurs during a lentivirus infection and how the distribution of multi-infection evolves during the disease course, we now determined the SIV copy numbers from splenocytes of 11 SIVmac251-infected rhesus macaques cross-sectionally covering the time span of primary infection throughout to end-stage immunodeficiency.
SIV multi-infection of single splenocytes was readily detected in all monkeys and all stages of the infection. Single-infected cells were more frequent than double- or triple- infected cells. There was no strong trend linking the copy number distribution to plasma viral load, disease stage, or CD4 cell counts.
SIV multi-infection of single cells is already established during the primary infection phase thus enabling recombination to affect viral evolution in vivo throughout the disease course.