Name
Identifying the Emv2-derived endogenous retroviral receptor in mouse vaginal tissue
Presenter
W. Austin Guild, University of British Columbia
Co-Author(s)
W. Austin Guild (1), Ananya Saraph (1), Jason Rogalski (2) and Maria Tokuyama (1) (1) Department of Microbiology and Immunology, University of British Columbia, Vancouver (2) Centre for Blood Research and Life Sciences Institute, University of British Columbia, Vancouver
Abstract Category
Breaking & Entering
Abstract
Endogenous retroviral sequences (ERV) sequences are among the 98% of our genome that have been deemed "junk DNA." ERVs make up 8% of the human genome and recent research indicates that these sequences contribute to disease and immunity. However, the potential effects of ERVs on antiviral immunity is not well studied. We previously found that a mouse ecotropic ERV derived from the Emv2 locus provides protection against vaginal herpes-simplex virus 2 (HSV-2) infection in mice, and this requires binding of the ERV envelope to the vaginal epithelium. We hypothesized that ERVs utilize receptors in the vaginal epithelium as an initial step in mediating protection against vaginal HSV-2 disease. To test this, we probed whether Emv-2 derived ERVs interact with the receptor for ecotropic murine leukemia virus (eMLV), cationic amino acid transporter-1 (mCAT1). Preliminary data showed that ERV entry into DFJ8 cells, an avian fibroblast cell line that is permissive to infectious ERVs, remained permissive after blocking mCAT1, suggesting that Emv2-derived ERVs enter cells through an alternative receptor. To identify potential receptors for ERVs, we co-immunoprecipitated (co-IP) ERVs and mouse vaginal tissue proteins using an antibody specific for the ERV-envelope protein and performed liquid chromatography mass spectrometry (LC-MS/MS) analysis on the eluates. Identified receptors were glucose receptor-1 (GLUT1), transferrin receptor-1 (TfR1), and mCAT1. GLUT1 has previously been associated with cell-to-cell transmission of human T-cell leukemia virus and TfR1 is the known entry receptor for mouse mammary tumor virus (MMTV). Thus, these receptors are promising candidates for being utilized by Emv2-derived ERVs.