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

// Man-Qing Liu 1 , Min Zhao 2 , Wen-Hua Kong 1 , Li Tang 1 , Fang Wang 1 , Ze-Rong Zhu 1 , Xia Wang 1 , Hong-Yan Qiu 2 , Dun-Jin Zhou 1 , Xu Wang 3 , Wen-Zhe Ho 3 , Wang Zhou 1 1 Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China 2 Wuhan Institute of Dermatology and Venereology, Wuhan 430030, China 3 Department 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 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.