BG1 has a major role in MHC-linked resistance to malignant lymphoma in the chicken
Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a mea...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 39; pp. 16740 - 16745 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
29.09.2009
National Acad Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Pathogen selection is postulated to drive MHC allelic diversity at loci for antigen presentation. However, readily apparent MHC infectious disease associations are rare in most species. The strong link between MHC-B haplotype and the occurrence of virally induced tumors in the chicken provides a means for defining the relationship between pathogen selection and MHC polymorphism. Here, we verified a significant difference in resistance to gallid herpesvirus-2 (GaHV-2)-induced lymphomas (Marek's disease) conferred by two closely-related recombinant MHC-B haplotypes. We mapped the crossover breakpoints that distinguish these haplotypes to the highly polymorphic BG1 locus. BG1 encodes an Ig-superfamily type I transmembrane receptor-like protein that contains an immunoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized by Src homology 2 domain-containing protein tyrosine phosphatase (SHP-2). The recombinant haplotypes are identical, except for differences within the BG1 3'-untranslated region (3'-UTR). The 3'-UTR of the BG1 allele associated with increased lymphoma contains a 225-bp insert of retroviral origin and showed greater inhibition of luciferase reporter gene translation compared to the other allele. These findings suggest that BG1 could affect the outcome of GaHV-2 infection through modulation of the lymphoid cell responsiveness to infection, a condition that is critical for GaHV-2 replication and in which the MHC-B haplotype has been previously implicated. This work provides a mechanism by which MHC-B region genetics contributes to the incidence of GaHV-2-induced malignant lymphoma in the chicken and invites consideration of the possibility that similar mechanisms might affect the incidence of lymphomas associated with other oncogenic viral infections. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Edited by Richard L. Witter, U.S. Department of Agriculture, East Lansing, MI, and approved August 10, 2009 Author contributions: R.M.G., Y.W., R.L.T., P.S.W., and M.M.M. designed research; R.M.G., Y.W., P.S.W., K.H., T.S., C.S.B., and M.M.M. performed research; R.L.T., P.S.W., K.H., T.S., and W.E.B. contributed new reagents/analytic tools; R.M.G., Y.W., R.L.T., P.S.W., K.H., T.S., and M.M.M. analyzed data; and R.L.T. and M.M.M. wrote the paper. 1R.M.G. and Y.W. contributed equally to this work. 2Present address: Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.0906776106 |