title: HIV‑1 downregulates the expression and phosphorylation of receptor tyrosine kinase by targeting the NF‑κB pathway.
abstract: Macrophages are major targets of human immunodeficiency virus (HIV) and can act as long‑term reservoirs of the virus. Chronic HIV‑1 infection is associated with dysregulated inflammation. Recepteur d'origine nantais (RON) is expressed in tissue resident macrophages and functions to maintain inflammatory homeostasis. The present study aimed to compare the expression of RON on HIV-positive and -negative participants, and to investigate the mechanism by which HIV‑1 influences the expression and function of RON in the JLTRG T cell line. The levels of RON and the RON ligand, macrophage‑stimulating protein (MSP), in the peripheral blood of HIV‑1-positive patients that were receiving (n=22) or not receiving highly active anti‑retroviral therapy (HAART) (n=82) and 37 healthy control participants were determined by enzyme‑linked immunosorbent assay. Expression of RON and MSP in the JLTRG T cell line was assessed by western blotting and the subcellular location was analyzed by fluorescence microscopy. JLTRG cells were co‑cultured with a cell line that stably expresses HIV, H9/HTLV‑IIIB, and alterations in the levels of RON and nuclear factor‑κB (NF‑κB) in JLTRG cells were assessed by western blotting. The expression of RON and MSP were significantly different in the serum of HIV‑1-positive patients that were receiving HAART compared with those not receiving HAART (P<0.05) and healthy control patients (P<0.01). RON was detected in JLTRG cells, and was shown to be downregulated by HIV‑1 infection. HIV‑1 infection of JLTRG cells also reduced NF‑κB phosphorylation. Thus, HIV‑1 was shown to downregulate the expression and phosphorylation of RON by targeting the NF‑κB pathway.
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Jianhe
authors.initials: J
authors.lastname: Gan
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Qin
authors.affiliation: Department of Infectious Disease, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Huang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Nanping
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Hu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Hangping
authors.initials: H
authors.lastname: Yao
mesh_terms: D000328:Adult; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B; D010766:Phosphorylation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases