title: EBI2 expression in B lymphocytes is controlled by the Epstein-Barr virus transcription factor, BRRF1 (Na), during viral infection.
abstract: Epstein-Barr virus-induced gene 2 (EBI2) is an important chemotactic receptor that is involved in proper B-cell T-cell interactions. Epstein-Barr virus (EBV) has been shown to upregulate this gene upon infection of cell lines, but the timing and mechanism of this upregulation, as well as its importance to EBV infection, remain unknown. This work investigated EBV's manipulation of EBI2 expression of primary naive B cells. EBV infection induces EBI2 expression resulting in elevated levels of EBI2 after 24 h until 7 days post-infection, followed by a dramatic decline (P=0.027). Increased EBI2 expression was not found in non-specifically stimulated B cells or when irradiated virus was used. The EBV lytic gene BRRF1 exhibited a similar expression pattern to EBI2 (R2=0.4622). BRRF1-deficient EBV could not induce EBI2. However, B cells transduced with BRRF1 showed elevated expression of EBI2 (P=0.042), a result that was not seen with transduction of a different EBV lytic transfection factor, BRLF1. Based on these results, we conclude that EBI2 expression is directly influenced by EBV infection and that BRRF1 is necessary and sufficient for EBI2 upregulation during infection.
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Caleb
authors.initials: C
authors.lastname: Cornaby
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Jillian L
authors.initials: JL
authors.lastname: Jafek
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Cameron
authors.initials: C
authors.lastname: Birrell
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Vera
authors.initials: V
authors.lastname: Mayhew
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Syndergaard
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Mella
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Wesley
authors.initials: W
authors.lastname: Cheney
authors.affiliation: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Poole
mesh_terms: D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D002465:Cell Movement; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C000618390:BRRF1 protein, Epstein-Barr virus; C080105:GPR183 protein, human; D043562:Receptors, G-Protein-Coupled; D015534:Trans-Activators; D014764:Viral Proteins