Respiratory syncytial virus blocks MHC Class-II surface translocation in human myeloid dendritic cell (B127)

Abstract

Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and young children. Antigen presentation by dendritic cells (DCs) is critical for the establishment of antiviral immunity and DCs are frequent target of viral immune evasion. Here we show that primary blood mDCs exposed in vitro to RSV failed to upregulate MHC Class-II. Similar results were observed in mDCs isolated from the nasal mucosa of RSV infected infants. MHC Class-II levels remained low despite the apparent upregulation of other markers of DC maturation such as MHC Class-I, CD83, CD86 and CD40. This inhibition could not be explained by the reduced bio-synthesis of MHC Class-II as class II transactivator (CIITA) level remained unchanged and the total cellular HLA-DR was comparable to flu exposed mDC. Furthermore, SDS stability assay showed similar level of MHC Class-II peptide complex between the two viral treatments, indicating RSV exposure did not block Class-II loading. Consistent with the reduced surface expression, confocal microscopy demonstrated a selective blockade of MHC Class-II surface translocation by RSV. These results demonstrate that RSV blocks DC antigen presentation by inhibiting Class-II peptide complex transport to the surface and suggest a mechanism of viral immune evasion. This work is supported by grants from Baylor Health Care Systems Foundation, the Children’s Medical Center of Dallas Foundation to MG, and the National Institutes of Health (K08 AI059379-02 to MG, U19 AIO57234 to JB).