title: Surfactant protein D inhibits HIV-1 infection of target cells via interference with gp120-CD4 interaction and modulates pro-inflammatory cytokine production.
abstract: Surfactant Protein SP-D, a member of the collectin family, is a pattern recognition protein, secreted by mucosal epithelial cells and has an important role in innate immunity against various pathogens. In this study, we confirm that native human SP-D and a recombinant fragment of human SP-D (rhSP-D) bind to gp120 of HIV-1 and significantly inhibit viral replication in vitro in a calcium and dose-dependent manner. We show, for the first time, that SP-D and rhSP-D act as potent inhibitors of HIV-1 entry in to target cells and block the interaction between CD4 and gp120 in a dose-dependent manner. The rhSP-D-mediated inhibition of viral replication was examined using three clinical isolates of HIV-1 and three target cells: Jurkat T cells, U937 monocytic cells and PBMCs. HIV-1 induced cytokine storm in the three target cells was significantly suppressed by rhSP-D. Phosphorylation of key kinases p38, Erk1/2 and AKT, which contribute to HIV-1 induced immune activation, was significantly reduced in vitro in the presence of rhSP-D. Notably, anti-HIV-1 activity of rhSP-D was retained in the presence of biological fluids such as cervico-vaginal lavage and seminal plasma. Our study illustrates the multi-faceted role of human SP-D against HIV-1 and potential of rhSP-D for immunotherapy to inhibit viral entry and immune activation in acute HIV infection.
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Hrishikesh
authors.initials: H
authors.lastname: Pandit
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Biomedical Informatics Centre, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Sonawani
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Brunel University, London, United Kingdom.
authors.forename: Asif S
authors.initials: AS
authors.lastname: Qaseem
authors.affiliation: Department of Obstetrics and Gynecology, Seth G S Medical College and K E M Hospital, Mumbai, Maharashtra, India.
authors.forename: Himangi
authors.initials: H
authors.lastname: Warke
authors.affiliation: Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Anushree
authors.initials: A
authors.lastname: Patil
authors.affiliation: Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Gajbhiye
authors.affiliation: Department of Clinical Research, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Immunocompromised Host Research Section, Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: Maha Ahmed
authors.initials: MA
authors.lastname: Al-Mozaini
authors.affiliation: Biomedical Informatics Centre, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Susan
authors.initials: S
authors.lastname: Idicula-Thomas
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Brunel University, London, United Kingdom.
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.affiliation: Department of Innate Immunity, National Institute for Research in Reproductive Health (ICMR), Mumbai, Maharashtra, India.
authors.forename: Taruna
authors.initials: T
authors.lastname: Madan
mesh_terms: D000328:Adult; D015704:CD4 Antigens / Q000737:chemistry / Q000378:metabolism*; D002584:Cervix Uteri / Q000821:virology; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D062105:Molecular Docking Simulation; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012661:Semen / Q000821:virology; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014621:Vagina / Q000821:virology; D053586:Virus Internalization / Q000187:drug effects
chemical_list: D015704:CD4 Antigens; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D037663:Pulmonary Surfactant-Associated Protein D; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases