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

PLoS One. 2012;7(9):e45706. doi: 10.1371/journal.pone.0045706. Epub 2012 Sep 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay / methods
  • Flow Cytometry / methods
  • Gene Expression Regulation, Viral*
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • Humans
  • Inflammation
  • Interleukins / biosynthesis*
  • Leukocytes, Mononuclear / cytology
  • Monocytes / cytology
  • Monocytes / virology
  • Real-Time Polymerase Chain Reaction / methods
  • env Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • IL27 protein, human
  • Interleukins
  • env Gene Products, Human Immunodeficiency Virus
  • gp130 envelope protein, Human immunodeficiency virus

Grant support

This research was supported by grants from Queen’s University (www.queensu.ca, grant number: N/A) and the National Sciences and Engineering Council of Canada (NSERC) (www.nserc-crsng.gc.ca/index_eng.as, grant number: 342168-07). CG has been supported by a studentship from the Ontario HIV Treatment Network (OHTN; www.ohtn.on.ca) and the Canadian Institutes of Health Research (CIHR) Vanier Scholarship (http://www.cihr-irsc.gc.ca/e/193.html). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.