title: The foamy virus genome remains unintegrated in the nuclei of G1/S phase-arrested cells, and integrase is critical for preintegration complex transport into the nucleus.
abstract: Foamy viruses are a member of the spumavirus subfamily of retroviruses with unique mechanisms of virus replication. Foamy virus replication is cell cycle dependent; however, the genome is found in the nuclei of cells arrested in the G(1)/S phase. Despite the presence of genome in the nuclei of growth-arrested cells, there is no viral gene expression, thus explaining its dependency on cell cycle. This report shows that the foamy virus genome remains unintegrated in G(1)/S phase-arrested cells. The foamy virus genome is detected by confocal microscopy in the nuclei of both dividing and growth-arrested cells. Alu PCR revealed foamy virus-specific DNA amplification from genomic DNA isolated in cycling cells at 24 h postinfection. In arrested cells no foamy virus DNA band was detected in cells harvested at 1 or 7 days after infection, and a very faint band that is significantly less than DNA amplified from cycling cells was observed at day 15. After these cells were arrested at the G(1)/S phase for 1, 7, or 15 days they were allowed to cycle, at which time foamy virus-specific DNA amplification was readily observed. Taken together, these results suggest that the foamy virus genome persists in nondividing cells without integrating. We have also established evidence for the first time that the foamy virus genome and Gag translocation into the nucleus are dependent on integrase in cycling cells, implicating the role of integrase in transport of the preintegration complex into the nucleus. Furthermore, despite the presence of a nuclear localization signal sequence in Gag, we observed no foamy virus Gag importation into the nucleus in the absence of integrase.
authors.affiliation: Department of Infectious Disease and Pathology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Yung-Tsun
authors.initials: YT
authors.lastname: Lo
authors.forename: Tao
authors.initials: T
authors.lastname: Tian
authors.forename: Peter E
authors.initials: PE
authors.lastname: Nadeau
authors.forename: Jeonghae
authors.initials: J
authors.lastname: Park
authors.forename: Ayalew
authors.initials: A
authors.lastname: Mergia
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000378:metabolism; D016679:Genome, Viral; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019426:Integrases / Q000235:genetics / Q000378:metabolism*; D012192:Retroviridae Infections; D016092:Spumavirus / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D019076:Transgenes; D016662:Virus Integration / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology
chemical_list: D004279:DNA, Viral; D015683:Gene Products, gag; D019426:Integrases