Norovirus antagonism of B-cell antigen presentation results in impaired control of acute infection.
Mucosal Immunol
; 9(6): 1559-1570, 2016 11.
Article
in En
| MEDLINE
| ID: mdl-27007673
ABSTRACT
Human noroviruses are a leading cause of gastroenteritis, and so, vaccine development is desperately needed. Elucidating viral mechanisms of immune antagonism can provide key insight into designing effective immunization platforms. We recently revealed that B cells are targets of norovirus infection. Because noroviruses can regulate antigen presentation by infected macrophages and B cells can function as antigen-presenting cells, we tested whether noroviruses regulate B-cell-mediated antigen presentation and the biological consequence of such regulation. Indeed, murine noroviruses could prevent B-cell expression of antigen presentation molecules and this directly correlated with impaired control of acute infection. In addition to B cells, acute control required MHC class I molecules, CD8+ T cells, and granzymes, supporting a model whereby B cells act as antigen presenting cells to activate cytotoxic CD8+ T cells. This immune pathway was active prior to the induction of antiviral antibody responses. As in macrophages, the minor structural protein VP2 regulated B-cell antigen presentation in a virus-specific manner. Commensal bacteria were not required for the activation of this pathway and ultimately only B cells were required for the clearance of viral infection. These findings provide new insight into the role of B cells in stimulating antiviral CD8+ T-cell responses.
Full text:
1
Collection:
01-internacional
Health context:
1_ASSA2030
/
3_ND
Database:
MEDLINE
Main subject:
B-Lymphocytes
/
Antigen Presentation
/
Caliciviridae Infections
/
Norovirus
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Mucosal Immunol
Year:
2016
Document type:
Article