title: Tubular cell HIV-entry through apoptosed CD4 T cells: a novel pathway.
abstract: We hypothesized that HIV-1 may enter tubular cells by phagocytosis of apoptotic fragments of HIV-1-infected T cells infiltrating tubular interstitium. The study was designed to evaluate the interaction of programmed death-1 (PD-1) receptors on CD4 T cells and programmed death ligand-1 (PD-L1) on tubular cells (HK2 and HRPTEC, primary tubular cells). Co-cultivation of HIV-1 infected lymphocytes (HIV-LY) with HK2s/HRPTECs resulted in T cell apoptosis, uptake of the apoptosed HIV-LY by HK2s/HRPTECs, tubular cell activation and HIV expression. Cytochalasin-B inhibited tubular cell HIV-LY uptake and anti-PD-L1 antibody inhibited HIV-LY apoptosis and tubular cell HIV-LY uptake, activation and HIV expression. These observations do indicate induction of apoptosis of T cells due to interaction of PD-1 and PD-L1 upon co-cultivation and subsequent phygocytosis of HIV-laden apoptotic bodies by tubular cells and thus the transfer of HIV-1 into tubular cells. These findings identify a novel pathway that facilitates HIV-1 entry into tubular cell.
authors.affiliation: Center for Excellence for Immunology and Inflammation, Feinstein Institute for Medical Research, Hofstra North Shore Long Island Jewish Medical School, New Hyde Park, NY, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.forename: Hersh
authors.initials: H
authors.lastname: Goel
authors.forename: Mohammad
authors.initials: M
authors.lastname: Husain
authors.forename: Xiqian
authors.initials: X
authors.lastname: Lan
authors.forename: Joanna
authors.initials: J
authors.lastname: Mikulak
authors.forename: Ashwani
authors.initials: A
authors.lastname: Malthotra
authors.forename: Saul
authors.initials: S
authors.lastname: Teichberg
authors.forename: Helena
authors.initials: H
authors.lastname: Schmidtmayerova
authors.forename: Pravin C
authors.initials: PC
authors.lastname: Singhal
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D010587:Phagocytosis; D053586:Virus Internalization