title: The simian immunodeficiency virus targets central cell cycle functions through transcriptional repression in vivo.
abstract: A massive and selective loss of CD4+ memory T cells occurs during the acute phase of immunodeficiency virus infections. The mechanism of this depletion is poorly understood but constitutes a key event with implications for progression. We assessed gene expression of purified T cells in Rhesus Macaques during acute SIVmac239 infection in order to define mechanisms of pathogenesis. We observe a general transcriptional program of over 1,600 interferon-stimulated genes induced in all T cells by the infection. Furthermore, we identify 113 transcriptional changes that are specific to virally infected cells. A striking downregulation of several key cell cycle regulator genes was observed and shared promotor-region E2F binding sites in downregulated genes suggested a targeted transcriptional control of an E2F regulated cell cycle program. In addition, the upregulation of the gene for the fundamental regulator of RNA polymerase II, TAF7, demonstrates that viral interference with the cell cycle and transcriptional regulation programs may be critical components during the establishment of a pathogenic infection in vivo.
authors: ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America. CMGH@novonordisk.com
authors: Carl-Magnus
authors: CM
authors: Hogerkorp
authors: Yoshiaki
authors: Y
authors: Nishimura
authors: Kaimei
authors: K
authors: Song
authors: Malcolm A
authors: MA
authors: Martin
authors: Mario
authors: M
authors: Roederer
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002453:Cell Cycle / Q000235:genetics*; D015536:Down-Regulation; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions / Q000235:genetics*; D008253:Macaca mulatta; D012097:Repressor Proteins; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D012097:Repressor Proteins