Microarray analysis of cytokine and chemokine genes in the brains of macaques with SHIV-encephalitis |
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Authors: | Sui Yongjun Potula Raghava Pinson David Adany Istvan Li Zhuang Day Jason Buch Eisha Segebrecht Jane Villinger Francois Liu Zhenqian Huang Mingzhao Narayan Opendra Buch Shilpa |
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Institution: | Department of Microbiology, Immunology and Molecular Genetics, Marion Merrell Dow Laboratory of Viral Pathogenesis, University of Kansas Medical Center, Kansas City, KS 66160, USA. |
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Abstract: | Human immunodeficiency virus (HIV)-encephalitis results from a cascade of viral-host interactions that lead to cytokine and chemokine imbalance, which then leads to neuropathologic manifestations of the disease. These include macrophage/microglia activation, astrocytosis and neuronal dysfunction or death. As the molecular mechanisms of this process are poorly understood, we used Atlas human cytokine or cytokine receptor microarray analysis to highlight gene expression profiles that accompanied encephalitis in Simian human immunodeficiency virus (SHIV) 89.6P-infected macaques. Of the 277 genes screened, marked upregulation of monocyte chemoattractant protein-1, interferon-inducible peptide IP-10 and interleukin-4 were observed specifically in the encephalitic brains. These genes are collectively known to promote macrophage infiltration and activation and virus replication. In contrast, genes regulating neurotrophic functions, such as brain-derived neurotrophic factor were downregulated. We also found that some of the apoptosis genes were up- or down-regulated. These data provide a comprehensive spectrum of gene expression that underscores the two major clinical manifestations of this unique syndrome: enhanced virus replication in brain macrophages and dystrophic changes in neurons. |
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Keywords: | chemokines cytokines neuropathology |
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