High-throughput gene expression profiling indicates dysregulation of intestinal cell cycle mediators and growth factors during primary simian immunodeficiency virus infection.
During primary simian immunodeficiency virus (SIV) infection, CD4+ T cells are severely depleted in gut-associated lymphoid tissue (GALT), while CD8+ T-cell numbers dramatically increase. To gain an understanding of the molecular basis of this disruption in T-cell homeostasis, host gene expression was monitored in longitudinal jejunum tissue biopsies from SIV-infected rhesus macaques by DNA microarray analysis. Transcription of cyclin E1, CDC2, retinoblastoma, transforming growth factor (TGF), fibroblast growth factor (FGF), and interleukin-2 was repressed while cyclins B1 and D2 and transcription factor E2F were upregulated, indicating a complex dysregulation of growth and proliferation within the intestinal mucosa. Innate, cell-mediated, and humoral immune responses were markedly upregulated in animals that significantly reduced their viral loads and retained more intestinal CD4+ T cells. We conclude that the alterations in intestinal gene expression during primary SIV infection were characteristic of a broad-range immune response, and reflective of the efficacy of viral suppression.
George
Michael D
MD
Department of Medical Microbiology and Immunology, University of California, Davis, Davis, CA 95616, USA.
Sankaran
Sumathi
S
Reay
Elizabeth
E
Gelli
Angie C
AC
Dandekar
Satya
S
D000818:Animals; D017951:Antigen Presentation; D002453:Cell Cycle / Q000235:genetics*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D008253:Macaca mulatta; D008297:Male; D012313:RNA / Q000032:analysis / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013312:Stress, Physiological / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology; D014158:Transcription, Genetic; D014766:Viremia / Q000235:genetics
D006133:Growth Substances; D012313:RNA