title: beta1 integrin expression increases susceptibility of memory B cells to Epstein-Barr virus infection.
abstract: Epstein-Barr virus (EBV) uses nasal mucosa-associated lymphoid tissue (NALT) as a portal of entry to establish life-long persistence in memory B cells. We previously showed that naïve and memory B cells from NALT are equally susceptible to EBV infection. Here we show that memory B cells from NALT are significantly more susceptible to EBV infection than those from remote lymphatic organs. We identify beta(1) integrin, which is expressed the most by naïve B cells of distinct lymphoid origin and by memory B cells from NALT, as a mediator of increased susceptibility to infection by EBV. Furthermore, we show that BMRF-2-beta(1) integrin interaction and the downstream signal transduction pathway are critical for postbinding events. An increase of beta(1) integrin expression in peripheral blood memory B cells provoked by CD40 stimulation plus B-cell receptor cross-linking increased the susceptibility of non-NALT memory B cells to EBV infection. Thus, EBV seems to utilize the increased activation status of memory B cells residing in the NALT to establish and ensure persistence.
authors.affiliation: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: Dorner
authors.forename: Franziska
authors.initials: F
authors.lastname: Zucol
authors.forename: Davide
authors.initials: D
authors.lastname: Alessi
authors.forename: Stephan K
authors.initials: SK
authors.lastname: Haerle
authors.forename: Walter
authors.initials: W
authors.lastname: Bossart
authors.forename: Markus
authors.initials: M
authors.lastname: Weber
authors.forename: Rahel
authors.initials: R
authors.lastname: Byland
authors.forename: Michele
authors.initials: M
authors.lastname: Bernasconi
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.forename: Sharof
authors.initials: S
authors.lastname: Tugizov
authors.forename: Roberto F
authors.initials: RF
authors.lastname: Speck
authors.forename: David
authors.initials: D
authors.lastname: Nadal
mesh_terms: D001402:B-Lymphocytes / Q000821:virology*; D002460:Cell Line; D004854:Herpesvirus 4, Human / Q000254:growth & development*; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000378:metabolism; D011485:Protein Binding; D025941:Protein Interaction Mapping; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism
chemical_list: C109482:BMRF-2 protein, Human herpesvirus 4; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D014764:Viral Proteins