Molecular Mimicry by Herpes Simplex Virus-Type 1: Autoimmune Disease After Viral Infection
10.1126/science.279.5355.1344
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
Abstract

Viral infection is sometimes associated with the initiation or exacerbation of autoimmune disease, although the underlying mechanisms remain unclear. One proposed mechanism is that viral determinants that mimic host antigens trigger self-reactive T cell clones to destroy host tissue. An epitope expressed by a coat protein of herpes simplex virus–type 1 (HSV-1) KOS strain has now been shown to be recognized by autoreactive T cells that target corneal antigens in a murine model of autoimmune herpes stromal keratitis. Mutant HSV-1 viruses that lacked this epitope did not induce autoimmune disease. Thus, expression of molecular mimics can influence the development of autoimmune disease after viral infection.

Bibliography

Zhao, Z.-S., Granucci, F., Yeh, L., Schaffer, P. A., & Cantor, H. (1998). Molecular Mimicry by Herpes Simplex Virus-Type 1: Autoimmune Disease After Viral Infection. Science, 279(5355), 1344–1347.

Authors 5
  1. Zi-Shan Zhao (first)
  2. Francesca Granucci (additional)
  3. Lily Yeh (additional)
  4. Priscilla A. Schaffer (additional)
  5. Harvey Cantor (additional)
References 32 Referenced 398
  1. Ridgway W. M., Weiner H. L., Fathman C. G., Curr. Opin. Immunol. 6, 946 (1994). (10.1016/0952-7915(94)90018-3) / Curr. Opin. Immunol. by Ridgway W. M. (1994)
  2. Dahlquist G., et al., Diabetologia 38, 1371 (1995); (10.1007/BF00401772) / Diabetologia by Dahlquist G. (1995)
  3. Challoner P. B., et al., Proc. Natl. Acad. Sci. U.S.A. 92, 7440 (1995); (10.1073/pnas.92.16.7440) / Proc. Natl. Acad. Sci. U.S.A. by Challoner P. B. (1995)
  4. ; S. Vento et al. Lancet 346 608 (1995). (10.1016/S0140-6736(95)91438-2)
  5. Sercarz E. E., et al., Annu. Rev. Immunol. 11, 729 (1993). (10.1146/annurev.iy.11.040193.003501) / Annu. Rev. Immunol. by Sercarz E. E. (1993)
  6. B. T. Rouse Adv. Virus Res. 47 353 (1996). (10.1016/S0065-3527(08)60739-3)
  7. M. B. A. Oldstone Cell 50 819 (1987) (10.1016/0092-8674(87)90507-1)
  8. M. G. von Herrath and M. B. A. Oldstone Curr. Opin. Immunol. 8 878 (1996). (10.1016/S0952-7915(96)80019-7)
  9. K. W. Wucherpfennig and J. L. Strominger Cell 80 695 (1995) (10.1016/0092-8674(95)90348-8)
  10. B. Hemmer et al. J. Exp. Med. 185 1651 (1997). (10.1084/jem.185.9.1651)
  11. M. B. A. Oldstone M. Nerenberg P. Southern J. Price H. Lewicki Cell 65 319 (1991); P. Ohashi et al. ibid. p. 305. (10.1016/0092-8674(91)90165-U)
  12. J. W. Streilein M. R. Dana B. R. Ksander Immunol. Today 18 443 (1997). (10.1016/S0167-5699(97)01114-6)
  13. A. C. Avery et al. Nature 376 431 (1995). (10.1038/376431a0)
  14. M. G. Niemialtowski and B. T. Rouse J. Immunol. 148 1864 (1992). (10.4049/jimmunol.148.6.1864)
  15. S. Friedman D. Sillcocks H. Cantor Immunogenetics 26 193 (1987). (10.1007/BF00346512)
  16. D. J. McGeoch et al. J. Gen. Virol. 69 1531 (1997)
  17. J. Hay and W. T. Ruyechan Curr. Topics Microbiol. Immunol. 179 1 (1992) (10.1007/978-3-642-77247-4_1)
  18. A. H. Patel and J. B. Maclean Virology 206 465 (1995). (10.1016/S0042-6822(95)80062-X)
  19. M. B. Raizman and C. S. Foster Curr. Eye Res. 7 823 (1988) (10.3109/02713688809033214)
  20. C. S. Foster et al. Ocular Immunol. Today (1990) p. 111.
  21. The KOS/UL6 m HSV-1 mutant was constructed by using a plasmid (pSG10) containing the UL6 gene within a 10.6-kb Eco RI-generated DNA fragment derived from the genome of HSV-1 strain KOS [A. L. Goldin et al. J. Virol. 38 50 (1981)]. A 1.9-kb Bgl II-Mfe I fragment from pSG10 containing a 1.3-kb segment encoding the UL6 NH 2 -terminal region was subcloned into the Bam HI-Eco RI sites of pBluescript
  22. (KS) (Stratagene) to produce the plasmid pZz. A single point mutation at position 15266 (C → T) of the UL6 gene was introduced with a site-directed mutagenesis kit (Clontech) and the mutant oligonucleotide 5′-GATTCTCCTACGGG T AGCTGGGGTATAC-3′ to generate a stop codon. This substitution was selected because it also eliminates the cleavage site for Pvu II (CAGCTG). The presence of the mutation in the pZz plasmid was confirmed by DNA sequencing with a Sequenase kit (U.S. Biochemical). For isolation of mutant virus Vero cell monolayers (6 × 10 5 cells per 60-mm dish) were incubated for 24 hours after seeding and then transfected with 12 μg of DNA (including 0.5 μg of infectious KOS DNA 5 μg of mutant plasmid DNA and 6.5 μg of carrier DNA). Five days later when generalized cytopathic effects were apparent cultures were harvested and then frozen and thawed three times. The cell suspension was sonicated briefly diluted 1:10 in medium passed through a 0.22-μm filter plated on monolayers of G33 cells-BHK21 cells expressing the UL6 protein [A. H. Patel et al. Virology 217 111 (1996)]-and overlaid with methylcellulose. After incubation at 37°C for 4 days plates were stained for 24 hours with medium containing neutral red individual plaques were picked and isolates were screened for their ability to produce cytopathic effects in G33 cells but not in Vero cells. Isolates with this phenotype were plaque-purified three times.
  23. Culture flasks (75 cm 2 ) were seeded at a density of 1 × 10 6 Vero cells per flask. Cells were infected with wild-type KOS or KOS/UL6 m mutant viruses at a multiplicity of infection of 10 PFU per cell. Uninfected and infected cells were harvested 18 to 20 hours after infection by scraping into the medium and were centrifuged at 1500 revolutions per minute and 4°C for 10 min. The cell pellet was resuspended in 5 ml of phosphate-buffered saline (PBS) repelleted and resuspended again in 1 ml of PBS. The cell suspension was stored at −70°C overnight thawed at 37°C and sonicated for 1 min. Samples were pelleted at 4°C for 10 min and the supernatant fluid was divided into aliquots and stored at −70°C. Protein concentrations were determined by measuring absorbance at 280 nm and using bovine serum albumin as a standard.
  24. A. M. McCarthy L. McMahon P. A. Schaffer J. Virol. 63 18 (1989). (10.1128/jvi.63.1.18-27.1989)
  25. W. Cai S. Person S. C. Warner J. Zhou N. A. DeLuca ibid. 61 714 (1987). (10.1128/jvi.61.3.714-721.1987)
  26. J. W. Streilein G. A. Wilbanks S. W. Cousins J. Neuroimmunol. 39 185 (1992). (10.1016/0165-5728(92)90253-H)
  27. Y. A. Akova J. Dutt A. Rodriguez N. Jabbur C. S. Foster Curr. Eye Res. 12 1093 (1993) (10.3109/02713689309033507)
  28. C. M. Mercadal D. M. Bouley D. DeStephano B. T. Rouse J. Virol. 67 3404 (1993). (10.1128/jvi.67.6.3404-3408.1993)
  29. M. von Herrath J. Dockter M. B. A. Oldstone Immunity 1 231 (1994). (10.1016/1074-7613(94)90101-5)
  30. The antigen used for in vitro stimulation was prepared from extracts of Vero cells infected with HSV-1 (KOS) (0.01 PFU per cell) and harvested 3 days after infection [W. Cai and P. A. Schaffer J. Virol. 66 2904 (1992)]. The virus suspension was inactivated by UV light (254 nm) for 20 min at a distance of 5 cm [L. Morrison and D. Knipe J. Virol. 68 689 (1994)]. Control antigen was prepared in the same way from extracts of uninfected cells.
  31. E. M. Opremcak et al. Invest. Ophthalmol. Vis. Sci. 29 749 (1988).
  32. We would like to thank D. Knipe for providing pSG10 A. H. Patel for G33 cells J. Glorioso for KO82 mutant virus and A. Angel for assistance in preparation of the manuscript. Supported by NIH grant AI 37562 to H.C.
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:37 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 12:57 a.m.)
Indexed 4 weeks, 1 day ago (July 30, 2025, 11:16 a.m.)
Issued 27 years, 6 months ago (Feb. 27, 1998)
Published 27 years, 6 months ago (Feb. 27, 1998)
Published Print 27 years, 6 months ago (Feb. 27, 1998)
Funders 0

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@article{Zhao_1998, title={Molecular Mimicry by Herpes Simplex Virus-Type 1: Autoimmune Disease After Viral Infection}, volume={279}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.279.5355.1344}, DOI={10.1126/science.279.5355.1344}, number={5355}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Zhao, Zi-Shan and Granucci, Francesca and Yeh, Lily and Schaffer, Priscilla A. and Cantor, Harvey}, year={1998}, month=feb, pages={1344–1347} }