Interleukin-27 is differentially associated with HIV viral load and CD4+ T cell counts in therapy-naïve HIV-mono-infected and HIV/HCV-co-infected Chinese.

Lai He,Hsiang-Fu Kung,Zheng-Rong Yang,Ming-Liang He,Yong-Xia Gan,Li Yang,Benny C Y Zee,Kenny K Y Siu,Maggie Haitian Wang,Lin Chen,Jin Zhao,William A Paxton

doi:10.1371/journal.pone.0096792

Abstract

Human Immunodeficiency Virus (HIV) infection and the resultant Acquired Immunodeficiency Syndrome (AIDS) epidemic are major global health challenges; hepatitis C virus (HCV) co-infection has made the HIV/AIDS epidemic even worse. Interleukin-27 (IL-27), a cytokine which inhibits HIV and HCV replication in vitro, associates with HIV infection and HIV/HCV co-infection in clinical settings. However, the impact of HIV and HCV viral loads on plasma IL-27 expression levels has not been well characterized. In this study, 155 antiretroviral therapy-naïve Chinese were recruited. Among them 80 were HIV- and HCV-negative healthy controls, 45 were HIV-mono-infected and 30 were HIV/HCV-co-infected. Plasma level HIV, HCV, IL-27 and CD4+ number were counted and their correlation, regression relationships were explored. We show that: plasma IL-27 level was significantly upregulated in HIV-mono-infected and HIV/HCV-co-infected Chinese; HIV viral load was negatively correlated with IL-27 titer in HIV-mono-infected subjects whereas the relationship was opposite in HIV/HCV-co-infected subjects; and the relationships between HIV viral loads, IL-27 titers and CD4+ T cell counts in the HIV mono-infection and HIV/HCV co-infection groups were dramatically different. Overall, our results suggest that IL-27 differs in treatment-naïve groups with HIV mono-infections and HIV/HCV co-infections, thereby providing critical information to be considered when caring and treating those with HIV mono-infection and HIV/HCV co-infection.

Highlights

Human Immunodeficiency Virus (HIV) causes progressive failure of the immune system which eventually leads to Acquired Immunodeficiency Syndrome (AIDS), and it is characterized by susceptibility to opportunistic infections and tumors
We showed that plasma IL-27 titer was elevated in HIV-positive individuals rather than in the health controls
This is consistent with previous reports describing the inhibition of HIV-1 replication by IL-27 and where the increased level of the cytokine is due to early stage immune response [19,23,25]

Summary

Introduction

HIV causes progressive failure of the immune system which eventually leads to AIDS, and it is characterized by susceptibility to opportunistic infections and tumors. Drug cocktails used in highly active antiretroviral therapy (HAART) significantly slow the progression of HIVinfected individuals to AIDS, HIV/AIDS is still one of the leading causes of death. HCV infection makes the HIV/AIDS epidemic much worse; this is because HCV co-infection facilitates HIV disease progression and increases the morbidity and mortality of AIDS patients [8,9,10]. In a cultured cell system, IL-27 induces IFN-c-like signals and induction of antiviral responses in hepatoma cells, hepatocytes and hepatic stellate cells [19,20]. It inhibits HCV in a dosedependent manner, indicating that IL-27 may be a potential

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