title: Combination antiretroviral therapy (cART) restores HIV-1 infection-mediated impairment of JAK-STAT signaling pathway.
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.
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Man-Qing
authors.initials: MQ
authors.lastname: Liu
authors.affiliation: Wuhan Institute of Dermatology and Venereology, Wuhan 430030, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Kong
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tang
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Ze-Rong
authors.initials: ZR
authors.lastname: Zhu
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: Wuhan Institute of Dermatology and Venereology, Wuhan 430030, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Qiu
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Dun-Jin
authors.initials: DJ
authors.lastname: Zhou
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19104, USA.
authors.forename: Wen-Zhe
authors.initials: WZ
authors.lastname: Ho
authors.affiliation: Wuhan Centers for Disease Prevention and Control, Wuhan 430015, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Zhou
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism; D008297:Male; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D050791:STAT Transcription Factors; D053612:Janus Kinases
keywords: HIV-1; JAK-STAT signaling pathway; combination antiretroviral therapy (cART); peripheral blood mononuclear cells (PBMCs)