RT Journal Article
SR Electronic
T1 Plasmacytoid dendritic cell sensing of hepatitis E virus is shaped by both viral and host factors
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202503256
DO 10.26508/lsa.202503256
VO 8
IS 6
A1 Joshi, Garima
A1 Décembre, Elodie
A1 Brocard, Jacques
A1 Montpellier, Claire
A1 Ferrié, Martin
A1 Allatif, Omran
A1 Mehnert, Ann-Kathrin
A1 Pons, Johann
A1 Galiana, Delphine
A1 Dao Thi, Viet Loan
A1 Jouvenet, Nolwenn
A1 Cocquerel, Laurence
A1 Dreux, Marlène
YR 2025
UL http://www.life-science-alliance.org/content/8/6/e202503256.abstract
AB Type I and III interferons critically protect the host against viral infection. Previous studies showed that IFN responses are suppressed in cells infected by hepatitis E virus (HEV). Here, we studied the anti-HEV function of IFN secreted by plasmacytoid dendritic cells (pDCs), specialized producers of IFNs. We showed that pDCs co-cultured with HEV-replicating cells secreted IFN in a cell contact–dependent manner. This pDC response required the endosomal nucleic acid sensor TLR7 and adhesion molecules. IFNs secreted by pDCs reduced viral spread. Intriguingly, ORF2, the capsid protein of HEV, can be produced in various forms by the infected cells, and we wanted to study their role in anti-HEV immune response. During infection, a fraction of ORF2 localizes into the nucleus, and glycosylated forms of ORF2 are massively secreted by infected cells. We showed that glycosylated ORF2 potentiates the recognition of infected cells by pDCs, by regulating cell contacts. On the other hand, nuclear ORF2 triggers immune response by IRF3 activation. Together, our results suggest that pDCs may be essential to control HEV replication.