Abstract:
:Costimulation is required for optimal T cell activation, yet it is unclear whether poxviruses dedicatedly subvert costimulation during infection. Here, we report that the secreted M2 protein encoded by cowpox virus (CPXV) specifically interacts with human and murine B7.1 (CD80) and B7.2 (CD86). We also show that M2 competes with CD28 and CTLA4 for binding to cell surface B7 ligands, with stronger efficacy against CD28. Functionally, recombinant M2 and culture supernatants from wild-type (WT) but not M2-deficient (∆M2) CPXV-infected cells can potently suppress B7 ligand-mediated T cell proliferation and interleukin-2 (IL-2) production. Furthermore, we observed increased antiviral CD4 and CD8 T cell responses in C57BL/6 mice challenged by ∆M2 CPXV compared with WT virus. These differences in immune responses to ∆M2 and WT CPXV were not observed in CD28-deficient mice. Taken together, our findings define a mechanism of viral sabotage of T cell activation that highlights the role of CD28 costimulation in host defense against poxvirus infections.
journal_name
Proc Natl Acad Sci U S Aauthors
Wang X,Piersma SJ,Elliott JI,Errico JM,Gainey MD,Yang L,Nelson CA,Yokoyama WM,Fremont DHdoi
10.1073/pnas.1909414116subject
Has Abstractpub_date
2019-10-15 00:00:00pages
21113-21119issue
42eissn
0027-8424issn
1091-6490pii
1909414116journal_volume
116pub_type
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