TY - JOUR
TI - Human rhinoviruses enter and induce proliferation of B lymphocytes
AU - Aab, A.
AU - Wirz, O.
AU - van de Veen, W.
AU - Söllner, S.
AU - Stanic, B.
AU - Rückert, B.
AU - Aniscenko, J.
AU - Edwards, M.R.
AU - Johnston, S.L.
AU - Papadopoulos, N.G.
AU - Rebane, A.
AU - Akdis, C.A.
AU - Akdis, M.
JO - Allergy: European Journal of Allergy and Clinical Immunology
PY - 2017
VL - 72
TODO - 2
SP - 232-243
PB - Wiley-Blackwell Publishing Ltd
SN - null
TODO - 10.1111/all.12931
TODO - alpha interferon;  CD19 antigen;  CD4 antigen;  CD8 antigen;  gamma interferon;  intercellular adhesion molecule 1;  interleukin 10;  interleukin 1beta;  interleukin 27;  interleukin 6;  macrophage inflammatory protein 1beta;  RANTES;  tumor necrosis factor;  virus RNA;  cytokine, Article;  B lymphocyte;  CD4+ T lymphocyte;  CD8+ T lymphocyte;  cell activation;  cell division;  cell population;  controlled study;  cytokine production;  cytotoxic T lymphocyte;  female;  flow cytometry;  HeLa cell line;  human;  human cell;  Human rhinovirus;  Human rhinovirus 29;  Human rhinovirus A16;  Human rhinovirus B14;  immune response;  immunofluorescence;  in situ hybridization;  in vitro study;  lymphocyte proliferation;  monocyte;  mononuclear cell;  nonhuman;  polymerase chain reaction;  priority journal;  virion;  virus entry;  virus inactivation;  virus replication;  B lymphocyte;  B lymphocyte subpopulation;  classification;  immunology;  lymphocyte activation;  male;  metabolism;  monocyte;  physiology;  picornavirus infection;  Rhinovirus;  serotype;  T lymphocyte subpopulation;  virology;  virus attachment;  virus entry, B-Lymphocyte Subsets;  B-Lymphocytes;  Cytokines;  Female;  Humans;  Leukocytes, Mononuclear;  Lymphocyte Activation;  Male;  Monocytes;  Picornaviridae Infections;  Rhinovirus;  Serogroup;  T-Lymphocyte Subsets;  Virus Attachment;  Virus Internalization;  Virus Replication
TODO - Background: Human rhinoviruses (HRVs) are one of the main causes of virus-induced asthma exacerbations. Infiltration of B lymphocytes into the subepithelial tissue of the lungs has been demonstrated during rhinovirus infection in allergic individuals. However, the mechanisms through which HRVs modulate the immune responses of monocytes and lymphocytes are not yet well described. Objective: To study the dynamics of virus uptake by monocytes and lymphocytes, and the ability of HRVs to induce the activation of in vitro-cultured human peripheral blood mononuclear cells. Methods: Flow cytometry was used for the enumeration and characterization of lymphocytes. Proliferation was estimated using 3H-thymidine or CFSE labeling and ICAM-1 blocking. We used bead-based multiplex assays and quantitative PCR for cytokine quantification. HRV accumulation and replication inside the B lymphocytes was detected by a combination of in situ hybridization (ISH), immunofluorescence, and PCR for positive-strand and negative-strand viral RNA. Cell images were acquired with imaging flow cytometry. Results: By means of imaging flow cytometry, we demonstrate a strong and quick binding of HRV types 16 and 1B to monocytes, and slower interaction of these HRVs with CD4+ T cells, CD8+ T cells, and CD19+ B cells. Importantly, we show that HRVs induce the proliferation of B cells, while the addition of anti-ICAM-1 antibody partially reduces this proliferation for HRV16. We prove with ISH that HRVs can enter B cells, form their viral replication centers, and the newly formed virions are able to infect HeLa cells. In addition, we demonstrate that similar to epithelial cells, HRVs induce the production of pro-inflammatory cytokines in PBMCs. Conclusion: Our results demonstrate for the first time that HRVs enter and form viral replication centers in B lymphocytes and induce the proliferation of B cells. Newly formed virions have the capacity to infect other cells (HeLa). These findings indicate that the regulation of human rhinovirus-induced B-cell responses could be a novel approach to develop therapeutics to treat the virus-induced exacerbation of asthma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
ER -