title: Investigation of Neuropathogenesis in HIV-1 Clade B and C Infection Associated with IL-33 and ST2 Regulation.
abstract: In present research work, for the first time, we demonstrate that neuropathogenesis in HIV-1 clade B and C infection is associated with IL-33 and ST2 dysregulation, that is, implication toward neuropathogenesis. It is known that neuropathogenesis of HIV infected individuals is clade dependent. Proinflammatory cytokines and related receptors play a significant role in the complex regulatory mechanisms of neuropathogenesis in HIV-1 infection. Among them, IL-33 is an inflammatory cytokine expressed in the central nervous system (CNS) and activates microglia cells and may affect neuroimmune inflammatory processes involved in HIV neuropathogenesis. Beside this, IL-33 receptor (ST2) plays a role in neuroinflammatory processes through the modulation of the biological action of IL-33. quantitative real time PCR (qRT-PCR), ELISA, Western blot (WB), and flow cytometry experiments were performed to elucidate the role of IL-33/ST2 in HIV neuropathogenesis in CNS cells. Apoptosis and mechanisms of IL-33 in neuronal cells were studied using caspase-3 assay and RT-PCR. Results of the studies suggest that the infection in CNS cells with HIV-1 clade B resulted in higher levels of IL-33/ST2L expression compared to HIV-1 clade C infection. Furthermore, higher concentrations of IL-33 were associated with a decrease in myocyte enhancer factor 2C (MEF2C) expression, a transcription factor that regulates synaptic function, and an increase in apoptosis, NOD2, and SLC11A1 in clade B infection. This led to neuroinflammation which dysregulates synaptic function and apoptosis. These parameters are common in neuroAIDS provoked by HIV infection.
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Adriana
authors.initials: A
authors.lastname: Yndart
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Ajeet
authors.initials: A
authors.lastname: Kaushik
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Marisela
authors.initials: M
authors.lastname: Agudelo
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Andrea
authors.initials: A
authors.lastname: Raymond
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Venkata S
authors.initials: VS
authors.lastname: Atluri
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology (CCMB), Uppal Road, Hyderabad 500007 (TS), India.
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Saxena
authors.affiliation: Center of Personalized Nanomedicine, Institute of Neuropharmacology, Department of Immunology, Herbert Wertheim College of Medicine, Florida International University , Miami, Florida 33199, United States.
authors.forename: Madhavan
authors.initials: M
authors.lastname: Nair
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1 / Q000145:classification; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33 / Q000008:administration & dosage / Q000378:metabolism*; D064326:MEF2 Transcription Factors / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D064326:MEF2 Transcription Factors; C578040:MEF2C protein, human; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: HIV-1; IL-33; Neuroinflammation; ST2; clade B; clade C; neuroAIDS; synaptic plasticity