Courtesy of Jessica Boname
Like the impossibly well-funded thieves from a good heist film, viruses pull immune-escape strategies from a deep bag of tricks. Murine γ-herpesvirus-68 (MHV-68) fine-tunes its attack on MHC class I molecules by degrading components of the complex that loads them with peptides.1
"There's the primary targeting of the class I heavy chain," says Jessica Boname, in Philip Stevenson's lab at the University of Cambridge, who showed previously that MHV-68's MK3 protein directs proteasomal degradation of MHC class I molecules. "But, there's also a direct effect," says Boname. MK3 targets components of the TAP complex, which normally loads peptides onto the MHCs.
MHC class I molecule assembly and cell-surface expression rely on peptide availability. By sabotaging peptide loading, MK3 undermines the MHC molecule indirectly as well as directly. This helps explain how MHV-68 can activate and replicate in B cells without being presented to CD8 T...