Viral interference with class II function

Abstract

We have previously demonstrated that classical (exogenous) MHC class II (MHCII)-restricted antigen processing is complemented by a complex endogenous processing network that, in the case of influenza, is a highly efficient source of peptides. Given this picture, it might be expected that some pathogens have adopted strategies to interfere with presentation of endogenously produced peptides. Indeed, this is the case for ectromelia (ECTV), the cause of mousepox. C15, a B22 family member encoded by the largest ECTV open reading frame, is a membrane glycoprotein expressed at the surface of the infected cell. Ablation of C15 results in substantial attenuation of the virus and enhanced ability to present processed antigen via MHCII but not MHC class I (MHCI). Conversely, expression of C15 alone is sufficient to inhibit MHCII-but not MHCI-restricted presentation of processed antigen and synthetic peptide. Imaging analysis suggests that C15 acts by disruption of the immunological synapse. Work toward additional mechanistic insights is ongoing.