Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection

Bibliographic Details
Title: Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection
Authors: Brigitta M. Laksono, Syriam Sooksawasdi Na Ayudhya, Muriel Aguilar-Bretones, Carmen W. E. Embregts, Gijsbert P. van Nierop, Debby van Riel
Source: mSphere, Vol 9, Iss 2 (2024)
Publisher Information: American Society for Microbiology, 2024.
Publication Year: 2024
Collection: LCC:Microbiology
Subject Terms: enterovirus D68, enterovirus, viral pathogenesis, systemic spread, extra-respiratory infection, immune cells, Microbiology, QR1-502
More Details: ABSTRACT Enterovirus D68 (EV-D68) is predominantly associated with mild respiratory infections, but can also cause severe respiratory disease and extra-respiratory complications, including acute flaccid myelitis. Systemic dissemination of EV-D68 is crucial for the development of extra-respiratory diseases, but it is currently unclear how EV-D68 spreads systemically (viremia). We hypothesize that immune cells contribute to the systemic dissemination of EV-D68, as this is a mechanism commonly used by other enteroviruses. Therefore, we investigated the susceptibility and permissiveness of human primary immune cells for different EV-D68 isolates. In human peripheral blood mononuclear cells inoculated with EV-D68, only B cells were susceptible but virus replication was limited. However, in B cell-rich cultures, such as Epstein–Barr virus-transformed B-lymphoblastoid cell line (BLCL) and primary lentivirus-transduced B cells, which better represent lymphoid B cells, were productively infected. Subsequently, we showed that dendritic cells (DCs), particularly immature DCs, are susceptible and permissive for EV-D68 infection and that they can spread EV-D68 to autologous BLCL. Altogether, our findings suggest that immune cells, especially B cells and DCs, could play an important role in the pathogenesis of EV-D68 infection. Infection of these cells may contribute to systemic dissemination of EV-D68, which is an essential step toward the development of extra-respiratory complications.IMPORTANCEEnterovirus D68 (EV-D68) is an emerging respiratory virus that has caused outbreaks worldwide since 2014. EV-D68 infects primarily respiratory epithelial cells resulting in mild respiratory diseases. However, EV-D68 infection is also associated with extra-respiratory complications, including polio-like paralysis. It is unclear how EV-D68 spreads systemically and infects other organs. We hypothesized that immune cells could play a role in the extra-respiratory spread of EV-D68. We showed that EV-D68 can infect and replicate in specific immune cells, that is, B cells and dendritic cells (DCs), and that virus could be transferred from DCs to B cells. Our data reveal a potential role of immune cells in the pathogenesis of EV-D68 infection. Intervention strategies that prevent EV-D68 infection of immune cells will therefore potentially prevent systemic spread of virus and thereby severe extra-respiratory complications.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2379-5042
Relation: https://doaj.org/toc/2379-5042
DOI: 10.1128/msphere.00526-23
Access URL: https://doaj.org/article/4aefe32870c84e29b26d938401a1af9c
Accession Number: edsdoj.4aefe32870c84e29b26d938401a1af9c
Database: Directory of Open Access Journals
More Details
ISSN:23795042
DOI:10.1128/msphere.00526-23
Published in:mSphere
Language:English