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Human rhinoviruses enter and induce proliferation of B lymphocytes
Author(s) -
Aab A.,
Wirz O.,
Veen W.,
Söllner S.,
Stanic B.,
Rückert B.,
Aniscenko J.,
Edwards M. R.,
Johnston S. L.,
Papadopoulos N. G.,
Rebane A.,
Akdis C. A.,
Akdis M.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12931
Subject(s) - biology , flow cytometry , rhinovirus , microbiology and biotechnology , peripheral blood mononuclear cell , virology , immunofluorescence , virus , viral replication , immune system , cd19 , antibody , in vitro , immunology , biochemistry
Abstract Background Human rhinoviruses ( HRV s) 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 HRV s 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 HRV s 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 3 H‐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 HRV s with CD 4+ T cells, CD 8+ T cells, and CD 19+ B cells. Importantly, we show that HRV s induce the proliferation of B cells, while the addition of anti‐ ICAM ‐1 antibody partially reduces this proliferation for HRV 16. We prove with ISH that HRV s 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, HRV s induce the production of pro‐inflammatory cytokines in PBMC s. Conclusion Our results demonstrate for the first time that HRV s 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.