IL-27-induced gene expression is downregulated in HIV-infected subjects.
OBJECTIVE
To characterize the effect of HIV infection on IL-27-induced gene expression.


METHODS
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.


CONCLUSIONS
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.
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Christina
C
Guzzo
Wilma M
WM
Hopman
Nor Fazila
NF
Che Mat
Wendy
W
Wobeser
Katrina
K
Gee
D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D007249:Inflammation; D007378:Interleukins / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009000:Monocytes / Q000166:cytology / Q000821:virology; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D054299:env Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D007378:Interleukins; C464565:MYDGF protein, human; D054299:env Gene Products, Human Immunodeficiency Virus; C083988:gp130 envelope protein, Human immunodeficiency virus