Oncotarget

Research Papers:

Combination antiretroviral therapy (cART) restores HIV-1 infection-mediated impairment of JAK-STAT signaling pathway

Man-Qing Liu, Min Zhao, Wen-Hua Kong, Li Tang, Fang Wang, Ze-Rong Zhu, Xia Wang, Hong-Yan Qiu, Dun-Jin Zhou, Xu Wang, Wen-Zhe Ho and Wang Zhou _

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Oncotarget. 2017; 8:22524-22533. https://doi.org/10.18632/oncotarget.15121

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Abstract

Man-Qing Liu1, Min Zhao2, Wen-Hua Kong1, Li Tang1, Fang Wang1, Ze-Rong Zhu1, Xia Wang1, Hong-Yan Qiu2, Dun-Jin Zhou1, Xu Wang3, Wen-Zhe Ho3, Wang Zhou1

1Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China

2Wuhan Institute of Dermatology and Venereology, Wuhan 430030, China

3Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA

Correspondence to:

Man-Qing Liu, email: liumq33@hotmail.com

Wang Zhou, email: rising-up@hotmail.com

Keywords: JAK-STAT signaling pathway, HIV-1, combination antiretroviral therapy (cART), peripheral blood mononuclear cells (PBMCs)

Received: August 11, 2016     Accepted: January 23, 2017     Published: February 06, 2017

ABSTRACT

JAK-STAT signaling pathway has a crucial role in host innate immunity against viral infections, including HIV-1. We therefore examined the impact of HIV-1 infection and combination antiretroviral therapy (cART) on JAK-STAT signaling pathway. Compared to age-matched healthy donors (n = 18), HIV-1-infected subjects (n = 18) prior to cART had significantly lower expression of toll-like receptors (TLR-1/4/6/7/8/9), the IFN regulatory factors (IRF-3/7/9), and the antiviral factors (OAS-1, MxA, A3G, PKR, and Tetherin). Three months’ cART partially restores the impaired functions of JAK-STAT-mediated antiviral immunity. We also found most factors had significantly positive correlations (p < 0.05) between each two factors in JAK-STAT pathway in healthy donors (98.25%, 168/171), but such significant positive associations were only found in small part of HIV-1-infected subjects (43.86%, 75/171), and stably increased during the cART (57.31%, 98/171 after 6 months’ cART). With regard to the restoration of some HIV-1 restriction factors, HIV-1-infected subjects who had CD4+ T cell counts > 350//μl responded better to cART than those with the counts < 350/μl. These findings indicate that the impairment of JAK-STAT pathway may play a role in the immunopathogenesis of HIV-1 disease.


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