PLoS ONE (Jan 2012)

IL-27-induced gene expression is downregulated in HIV-infected subjects.

  • Christina Guzzo,
  • Wilma M Hopman,
  • Nor Fazila Che Mat,
  • Wendy Wobeser,
  • Katrina Gee

DOI
https://doi.org/10.1371/journal.pone.0045706
Journal volume & issue
Vol. 7, no. 9
p. e45706

Abstract

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OBJECTIVE: To characterize the effect of HIV infection on IL-27-induced gene expression. DESIGN: During HIV infection, cytokine expression and function become deregulated. IL-27 is an important modulator of inflammatory responses. Interestingly, IL-27 can inhibit HIV replication in T cells and monocytes, implicating IL-27 as a potential adjunct to anti-viral treatment. Our previous work demonstrated that circulating HIV may suppress IL-27 expression, therefore, this study, in continuation of our previous work, aimed to understand how HIV affects expression levels of the IL-27 receptor and downstream functions of IL-27. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood of HIV negative and HIV positive (viremic) individuals to assess IL-27-induced gene expression by flow cytometry and ELISA. PBMC were also processed for monocyte enrichment to assess IL-27 receptor expression by flow cytometry and real-time PCR. RESULTS: Expression of the IL-27 receptor subunit, gp130, was upregulated in response to IL-27 in HIV negative individuals, however, in HIV positive individuals, this IL-27 response was diminished. Furthermore, we observed downregulation of IL-27-induced IL-6, TNF-α, and IL-10 expression in HIV positive subjects. CONCLUSION: In HIV infection, IL-27-induced gene expression was impaired, indicating HIV-mediated dysregulation of IL-27 functions occurs during HIV infection. This study provides evidence for new viral pathogenic mechanisms contributing to the widespread impairment of immune responses observed in HIV pathogenesis.