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    Poster Networking

    Hemostatic Systems in Cancer, Inflammation and Immunity

    Poster Networking Session

    PB0725 - Tissue factor on human immunodeficiency virus and dengue virus as the molecular basis for hemostatic pathology

    Monday, June 26, 2023
    18:30 – 19:30 ET
    Room: Exhibition

      Presenting Author(s)

    • Henry E. West (he/him/his)

      Graduate Student
      University of British Columbia
      Vancouver, British Columbia, Canada

      • Co-Author(s)

    • BL

      Bryan H. Lin

      Postdoctoral Fellow
      University of British Columbia
      Vancouver, British Columbia, Canada

    • MS

      Michael R. Sutherland

      Research Associate
      Canadian Blood Services
      Vancouver, British Columbia, Canada

    • CL

      Cindy Lam

      Graduate Student
      University of British Columbia
      Vancouver, British Columbia, Canada

    • JM

      James H. Morrissey

      Professor
      University of Michigan
      Ann Arbor, Michigan, United States

    • IS

      Ivan Sadowski

      Professor
      University of British Columbia
      Vancouver, British Columbia, Canada

    • MH

      Marc Horwitz

      Professor
      University of British Columbia
      Vancouver, British Columbia, Canada

    • Edward L. Pryzdial, PhD

      Clinical Professor | Senior Scientist
      University of British Columbia | Canadian Blood Services
      Vancouver, British Columbia, Canada

    Background: Numerous viruses modulate blood clotting leading to hemostatic pathology. A molecular explanation for these events does not exist. Our objective is to fill this knowledge gap and unify the molecular basis. Here we focus on two viruses that differently affect hemostasis; human immunodeficiency virus (HIV), which is thrombotic, and dengue virus (DENV), which is hemorrhagic.

    We have observed the host-encoded coagulation initiator, tissue factor (TF), on the surface of various purified herpes viruses. Common to these viruses is an envelope, an outer membrane obtained from host cells that can retain host proteins like TF. Since TF is widely expressed on infectible cell types, we hypothesize that TF is ubiquitous on enveloped viruses and influences viral pathology.

    Aims: 1. Demonstrate TF antigen on the envelope of HIV and DENV
    2. Demonstrate TF coagulation activity associated with HIV and DENV

    Methods: Immunogold electron microscopy was performed to show TF and viral antigens. A chromogenic assay probed the TF- and factor (F) VIIa-dependent activation of FX to FXa. Plasma clotting assays were conducted using purified virus as a coagulation initiator. Anti-TF antibodies or NAPc2 confirmed the involvement of TF function.

    Results: TF was detected on purified lab strain grown (lsg)-DENV, which co-stained for virus-encoded E protein, confirming virus identity. TF was found on viral particles in lsg-HIV samples. Although of proper size and morphology, these were not co-identified by currently available anti-gp120 antibodies. TF antigen was identified on HIV derived from the plasma of a viremic patient, which co-stained with anti-gp120. lsg-DENV or lsg-HIV resulted in dose-dependent increased FXa generation and shortening of clotting time. These were inhibitable by TF-specific agents and required FVIIa and calcium.

    Conclusion(s): These data support TF on the surface of HIV and DENV, expanding the spectrum of viruses known to harbor TF and explain the molecular basis of pathology during infection.