The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Sequence motifs in adenoviral DNA block immune activation by stimulatory CpG motifs
Open accessAbstract
Unmethylated CpG dinucleotides in particular base contexts (CpG-S motifs) are relatively common in bacterial DNA but are rare in vertebrate DNA. B cells and monocytes have the ability to detect such CpG-S motifs that trigger innate immune defenses with production of Th1-like cytokines. Despite comparable levels of unmethylated CpG dinucleotides, DNA from serotype 12 adenovirus is immune-stimulatory, but serotype 2 is nonstimulatory and can even inhibit activation by bacterial DNA. In type 12 genomes, the distribution of CpG-flanking bases is similar to that predicted by chance. However, in type 2 adenoviral DNA the immune stimulatory CpG-S motifs are outnumbered by a 15- to 30-fold excess of CpG dinucleotides in clusters of direct repeats or with a C on the 5′ side or a G on the 3′ side. Synthetic oligodeoxynucleotides containing these putative neutralizing (CpG-N) motifs block immune activation by CpG-S motifs in vitro and in vivo. Eliminating 52 of the 134 CpG-N motifs present in a DNA vaccine markedly enhanced its Th1-like function in vivo, which was increased further by the addition of CpG-S motifs. Thus, depending on the CpG motif, prokaryotic DNA can be either immune-stimulatory or neutralizing. These results have important implications for understanding microbial pathogenesis and molecular evolution and for the clinical development of DNA vaccines and gene therapy vectors.
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Cites
CpG motifs in bacterial DNA trigger direct B-cell activation
Krieg, A. M., Yi, A.-K., Matson, S., Waldschmidt, T. J., Bishop, G. A., Teasdale, R., Koretzky, G. A., & Klinman, D. M. (1995) · Nature · doi:10.1038/374546a0 · Cited by 3,508
Self-citationKlinman, D. M., Yi, A. K., Beaucage, S. L., Conover, J., & Krieg, A. M. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.7.2879 · Cited by 1,477
Self-citationImmunostimulatory DNA Sequences Necessary for Effective Intradermal Gene Immunization
Sato, Y., Roman, M., Tighe, H., Lee, D., Corr, M., Nguyen, M.-D., Silverman, G. J., Lotz, M., Carson, D. A., & Raz, E. (1996) · Science · doi:10.1126/science.273.5273.352 · Cited by 1,058
CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity
Chu, R. S., Targoni, O. S., Krieg, A. M., Lehmann, P. V., & Harding, C. V. (1997) · The Journal of Experimental Medicine · doi:10.1084/jem.186.10.1623 · Cited by 1,002
Self-citationDonnelly, J. J., Ulmer, J. B., Shiver, J. W., & Liu, M. A. (1997) · Annual Review of Immunology · doi:10.1146/annurev.immunol.15.1.617 · Cited by 987
Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants
Roman, M., Martin-Orozco, E., Goodman, J. S., Nguyen, M.-D., Sato, Y., Ronaghy, A., Kornbluth, R. S., Richman, D. D., Carson, D. A., & Raz, E. (1997) · Nature Medicine · doi:10.1038/nm0897-849 · Cited by 908
Ballas, Z. K., Rasmussen, W. L., & Krieg, A. M. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.1840 · Cited by 754
Self-citationCpG islands as gene markers in the vertebrate nucleus
Bird, A. P. (1987) · Trends in Genetics · doi:10.1016/0168-9525(87)90294-0 · Cited by 678
Davis, H. L., Weeranta, R., Waldschmidt, T. J., Tygrett, L., Schorr, J., & Krieg, A. M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.2.870 · Cited by 677
Self-citationMacrophages ingest and are activated by bacterial DNA
Stacey, K. J., Sweet, M. J., & Hume, D. A. (1996) · The Journal of Immunology · doi:10.4049/jimmunol.157.5.2116 · Cited by 570
Cited by
CpG Motifs in Bacterial DNA and Their Immune Effects
Krieg, A. M. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.100301.064842 · Cited by 2,573
Self-citationTherapeutic potential of Toll-like receptor 9 activation
Krieg, A. M. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd2059 · Cited by 1,246
Self-citationDNA Vaccines: Immunology, Application, and Optimization
Gurunathan, S., Klinman, D. M., & Seder, R. A. (2000) · Annual Review of Immunology · doi:10.1146/annurev.immunol.18.1.927 · Cited by 1,207
Toll-like receptors in systemic autoimmune disease
Marshak-Rothstein, A. (2006) · Nature Reviews Immunology · doi:10.1038/nri1957 · Cited by 1,116
Barrat, F. J., Meeker, T., Gregorio, J., Chan, J. H., Uematsu, S., Akira, S., Chang, B., Duramad, O., & Coffman, R. L. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20050914 · Cited by 928
Metadata
- Authors
- Krieg, A. M., Wu, T., Weeratna, R., Efler, S. M., Love-Homan, L., Yang, L., Yi, A.-K., Short, D., & Davis, H. L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-10-13
- Volume
- 95
- Issue
- 21
- Pages
- 12631-12636
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2054654286
- Cited by
- 397
- References
- 48
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- green
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