Impact of antiretroviral treatment on gene expression in peripheral blood mononuclear cells from SIVmac251-infected macaques.
BACKGROUND
A survey of gene expression in peripheral blood mononuclear cells from cynomolgus macaques infected with SIVmac251 was conducted to ascertain the impact of viral infection and successful antiretroviral (ARV) intervention on gene transcription at peak seroconversion, viral set point, and after treatment with 9-R 2 phosphonomethoxypropyl adenine and beta -2'3' dideoxy-3'-thia-5 fluorocytidine.


METHODS
Robust multichip average-normalized data sets generated on Affymetrix GeneChips were analyzed using Significance Analysis of Microarrays (SAM), to determine differential gene expression. Unsupervised learning algorithms and gene-ontology tools were used to elucidate hierarchical relationships and to define the function of significantly enriched biological categories of differentially regulated genes. Gene networks associated with immune response and inflammation impacted by ARV treatment were derived by use of Pathway Architect software.


RESULTS
Viral infection results in down-regulation of gene expression, which is greatest by the viral set point. Of the 3647 genes down-regulated at the viral set point, 1033 were up-regulated as the result of successful ARV treatment. There is significant overlap in the identity of these genes.


CONCLUSIONS
Intervention with successful ARV treatment in macaques infected with SIVmac251 results in the partial reversal of the down-regulated gene expression characteristic of early viral infection.
Vahey
Maryanne T
MT
Division of Retrovirology, Walter Reed Army Institute of Research, Washington, DC, USA. mvahey@hivresearch.org
Ockenhouse
Christian F
CF
Wang
Zhining
Z
Yalley-Ogunro
Jake
J
Greenhouse
Jack
J
Nau
Martin E
ME
Lewis
Mark G
MG
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000821:virology; D008252:Macaca fascicularis; D010802:Phylogeny; D016097:Simian Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D015302:Simian Immunodeficiency Virus; D013997:Time Factors; D019562:Viral Load
D000998:Antiviral Agents