Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection
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 di...
| Główni autorzy: | , , , , , |
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| Format: | Artykuł |
| Język: | English |
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American Society for Microbiology
2024-02-01
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| Seria: | mSphere |
| Hasła przedmiotowe: | |
| Dostęp online: | https://journals.asm.org/doi/10.1128/msphere.00526-23 |
| _version_ | 1827150230993240064 |
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| author | Brigitta M. Laksono Syriam Sooksawasdi Na Ayudhya Muriel Aguilar-Bretones Carmen W. E. Embregts Gijsbert P. van Nierop Debby van Riel |
| author_facet | Brigitta M. Laksono Syriam Sooksawasdi Na Ayudhya Muriel Aguilar-Bretones Carmen W. E. Embregts Gijsbert P. van Nierop Debby van Riel |
| author_sort | Brigitta M. Laksono |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-07T19:57:56Z |
| format | Article |
| id | doaj.art-4aefe32870c84e29b26d938401a1af9c |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2025-03-20T21:30:47Z |
| publishDate | 2024-02-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-4aefe32870c84e29b26d938401a1af9c2024-08-11T18:42:30ZengAmerican Society for MicrobiologymSphere2379-50422024-02-019210.1128/msphere.00526-23Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infectionBrigitta M. Laksono0Syriam Sooksawasdi Na Ayudhya1Muriel Aguilar-Bretones2Carmen W. E. Embregts3Gijsbert P. van Nierop4Debby van Riel5Department of Viroscience, Erasmus MC, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC, Rotterdam, the NetherlandsDepartment of Viroscience, Erasmus MC, Rotterdam, the NetherlandsABSTRACT 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.https://journals.asm.org/doi/10.1128/msphere.00526-23enterovirus D68enterovirusviral pathogenesissystemic spreadextra-respiratory infectionimmune cells |
| spellingShingle | Brigitta M. Laksono Syriam Sooksawasdi Na Ayudhya Muriel Aguilar-Bretones Carmen W. E. Embregts Gijsbert P. van Nierop Debby van Riel Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection mSphere enterovirus D68 enterovirus viral pathogenesis systemic spread extra-respiratory infection immune cells |
| title | Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection |
| title_full | Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection |
| title_fullStr | Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection |
| title_full_unstemmed | Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection |
| title_short | Human B cells and dendritic cells are susceptible and permissive to enterovirus D68 infection |
| title_sort | human b cells and dendritic cells are susceptible and permissive to enterovirus d68 infection |
| topic | enterovirus D68 enterovirus viral pathogenesis systemic spread extra-respiratory infection immune cells |
| url | https://journals.asm.org/doi/10.1128/msphere.00526-23 |
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