Gene expression profiling of host response in models of acute HIV infection.
HIV infection is characterized by a host response composed of adaptive and innate immunity that partially limits viral replication; however, it ultimately fails in eradicating the virus. To model host gene expression during acute HIV infection, we infected cynomolgus macaques with the SIV/HIV-1 chimeric virus, SHIV89.6P, and profiled gene expression in peripheral blood over a 5-wk period using a high density cDNA microarray. We demonstrate that viral challenge induced a widespread suppression of genes regulating innate immunity, including the LPS receptors, CD14 and TLR4. An overexpression of 16 IFN-stimulated genes was also observed in response to infection; however, it did not correlate with control over viral titers. A statistical analysis of the dataset identified 10 genes regulating apoptosis with differential expression during the first 2 wk of infection (p < 0.004). Quantitative real-time PCR verified transcriptional increases in IFN-alpha-inducible genes and decreases in genes regulating innate immunity. Therefore, the persistence of high viral loads despite an extensive IFN response suggests that HIV can resist in vivo IFN treatment despite published reports of in vitro efficacy. The transcriptional suppression of genes regulating innate immunity may allow HIV to evade acute host responses and establish a chronic infection and may reduce innate host defense against opportunistic infections.
Bosinger
Steven E
SE
Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Hosiawa
Karoline A
KA
Cameron
Mark J
MJ
Persad
Desmond
D
Ran
Longsi
L
Xu
Luoling
L
Boulassel
Mohamed R
MR
Parenteau
Monique
M
Fournier
Jocelyn
J
Rud
Erling W
EW
Kelvin
David J
DJ
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D020869:Gene Expression Profiling / Q000379:methods*; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics; D007370:Interferon Type I / Q000096:biosynthesis; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014779:Virus Replication / Q000276:immunology
D007370:Interferon Type I