Acute SIV infection of the brain leads to upregulation of IL6 and interferon-regulated genes: expression patterns throughout disease progression and impact on neuroAIDS.
The virus/host interactions during the acute phase of human immunodeficiency virus (HIV) infection help determine the course of disease. During this time period, virus enters the brain. Here, we report clusters of genes whose transcripts are significantly upregulated in the frontal lobe of the brain during acute simian immunodeficiency virus (SIV) infection of rhesus monkeys. Many of these genes are involved in interferon (IFN) and/or interleukin (IL)-6 pathways. Although neither IFNalpha nor IFNgamma are elevated in the brain, IL6 is increased. Both IFNalpha and IL6 are elevated in plasma during this acute phase. The upregulation of STAT1, verified by immunohistochemical staining, can be due to both central nervous system (CNS) (SIV and IL6) and peripheral (IFNalpha and IL6) causes, and can itself drive the expression of many of these genes. Examination of the levels of expression of the upregulated genes in the post-acute and long-term phases of infection, as well as in SIV encephalitis, reveals increased expression throughout SIV infection, which may serve to protect the brain, but can have untoward long-term consequences.
Roberts
Eleanor S
ES
Department of Neuropharmacology, CVN-1, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Burudi
E M E
EM
Flynn
Claudia
C
Madden
Lisa J
LJ
Roinick
Kelli L
KL
Watry
Debbie D
DD
Zandonatti
Michelle A
MA
Taffe
Michael A
MA
Fox
Howard S
HS
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007372:Interferons / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008253:Macaca mulatta; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050794:STAT1 Transcription Factor; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D015854:Up-Regulation; D019562:Viral Load / Q000379:methods
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007372:Interferons