beta1 integrin expression increases susceptibility of memory B cells to Epstein-Barr virus infection.
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.
Dorner
Marcus
M
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland.
Zucol
Franziska
F
Alessi
Davide
D
Haerle
Stephan K
SK
Bossart
Walter
W
Weber
Markus
M
Byland
Rahel
R
Bernasconi
Michele
M
Berger
Christoph
C
Tugizov
Sharof
S
Speck
Roberto F
RF
Nadal
David
D
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
C109482:BMRF-2 protein, Human herpesvirus 4; D019012:Integrin beta1; D008562:Membrane Glycoproteins; D014764:Viral Proteins