title: Stable multi-infection of splenocytes during SIV infection--the basis for continuous recombination.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Virology, Saarland University, Homburg D-66421, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schultz
authors.forename: Sieghart
authors.initials: S
authors.lastname: Sopper
authors.forename: Ulrike
authors.initials: U
authors.lastname: Sauermann
authors.forename: Andreas
authors.initials: A
authors.lastname: Meyerhans
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Suspène
mesh_terms: D000818:Animals; D018628:Gene Dosage; D008253:Macaca mulatta; D011533:Proviruses / Q000235:genetics; D011995:Recombination, Genetic; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000821:virology*; D015163:Superinfection / Q000821:virology*; D016662:Virus Integration