Broadly Reactive Human CD8 T Cells that Recognize an Epitope Conserved between VZV, HSV and EBV
Human herpesviruses can cause a wide range of serious infections. They are extremely common and individuals remain latently infected lifelong, with reactivations often causing recurrent or severe disease. T-cells are important in controlling herpesvirus infections and preventing their reactivation, so vaccines that induce T-cells are likely to improve control. Here, we examined human T-cells against VZV that might allow focused vaccine development. We identified a dominant target against which the majority of subjects had mounted a CD8 T-cell response. We found that very similar targets also exist in three other important herpesviruses, HSV-1, HSV-2 and EBV. We showed that CD8 T-cells recognizing the VZV target could also recognize the others and we hypothesized that recurrent encounter with these viruses could boost this common response. In some individuals, immunization with a VZV vaccine did cause activation of these cells, but in most it did not. This reflects the variable efficacy of the currently available VZV vaccine. Our findings suggest that T-cell targets may be shared between herpesvirus species and may therefore contribute to a novel “pan-herpesvirus” vaccine. However, current VZV vaccines cannot reliably stimulate these T-cells and new strategies will be necessary to achieve this goal.
Vyšlo v časopise:
Broadly Reactive Human CD8 T Cells that Recognize an Epitope Conserved between VZV, HSV and EBV. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004008
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004008
Souhrn
Human herpesviruses can cause a wide range of serious infections. They are extremely common and individuals remain latently infected lifelong, with reactivations often causing recurrent or severe disease. T-cells are important in controlling herpesvirus infections and preventing their reactivation, so vaccines that induce T-cells are likely to improve control. Here, we examined human T-cells against VZV that might allow focused vaccine development. We identified a dominant target against which the majority of subjects had mounted a CD8 T-cell response. We found that very similar targets also exist in three other important herpesviruses, HSV-1, HSV-2 and EBV. We showed that CD8 T-cells recognizing the VZV target could also recognize the others and we hypothesized that recurrent encounter with these viruses could boost this common response. In some individuals, immunization with a VZV vaccine did cause activation of these cells, but in most it did not. This reflects the variable efficacy of the currently available VZV vaccine. Our findings suggest that T-cell targets may be shared between herpesvirus species and may therefore contribute to a novel “pan-herpesvirus” vaccine. However, current VZV vaccines cannot reliably stimulate these T-cells and new strategies will be necessary to achieve this goal.
Zdroje
1. Fields BN, Knipe DM, Howley PM, editors (2007) Fields' Virology. London: Wolters Kluwer/Lippincott Williams & Wilkins. 2664 p.
2. WilsonA, SharpM, KoropchakCM, TingSF, ArvinAM (1992) Subclinical Varicella-Zoster Virus Viremia, Herpes Zoster, and T Lymphocyte Immunity to Varicella-Zoster Viral Antigens after Bone Marrow Transplantation. J Infect Dis 165: 119–126.
3. MehtaSK, CohrsRJ, ForghaniB, ZerbeG, GildenDH, et al. (2004) Stress-induced subclinical reactivation of varicella zoster virus in astronauts. Journal of Medical Virology 72: 174–179.
4. PapaevangelouV, QuinlivanM, LockwoodJ, PapaloukasO, SideriG, et al. (2013) Subclinical VZV reactivation in immunocompetent children hospitalized in the ICU associated with prolonged fever duration. Clin Microbiol Infect 19: E245–51.
5. WeinbergA, LevinMJ (2010) VZV T cell-mediated immunity. Curr Top Microbiol Immunol 342: 341–357.
6. ArvinAM (1996) Immune responses to varicella-zoster virus. Infect Dis Clin North Am 10: 529–570.
7. GoodRA, ZakSJ (1956) Disturbances in gamma globulin synthesis as experiments of nature. Pediatrics 18: 109–149.
8. Patterson-BartlettJ, LevinMJ, LangN, SchödelFP, VesseyR, et al. (2007) Phenotypic and functional characterization of ex vivo T cell responses to the live attenuated herpes zoster vaccine. Vaccine 25: 7087–7093.
9. OxmanMN (2010) Zoster Vaccine: Current Status and Future Prospects. Clin Infect Dis 51: 197–213.
10. DiazPS, SmithS, HunterE, ArvinAM (1989) T lymphocyte cytotoxicity with natural varicella-zoster virus infection and after immunization with live attenuated varicella vaccine. J Immunol 142: 636–641.
11. LevinMJ, MurrayM, RotbartHA, ZerbeGO, WhiteCJ, et al. (1992) Immune Response of Elderly Individuals to a Live Attenuated Varicella Vaccine. J Infect Dis 166: 253–259.
12. LevinMJ, MurrayM, ZerbeGO, WhiteCJ, HaywardAR (1994) Immune Responses Of Elderly Persons 4 Years After Receiving A Live Attenuated Varicella Vaccine. J Infect Dis 170: 522–526.
13. OxmanMN, LevinMJ, JohnsonGR, SchmaderKE, StrausSE, et al. (2005) A Vaccine to Prevent Herpes Zoster and Postherpetic Neuralgia in Older Adults. New England Journal of Medicine 352: 2271–2284.
14. FreyCR, SharpMA, MinAS, SchmidDS, LoparevV, et al. (2003) Identification of CD8+ T Cell Epitopes in the Immediate Early 62 Protein (IE62) of Varicella-Zoster Virus, and Evaluation of Frequency of CD8+ T Cell Response to IE62, by Use of IE62 Peptides after Varicella Vaccination. J Infect Dis 188: 40–52.
15. HarariA, EndersFB, CelleraiC, BartP-A, PantaleoG (2009) Distinct Profiles of Cytotoxic Granules in Memory CD8 T Cells Correlate with Function, Differentiation Stage, and Antigen Exposure. J Virol 83: 2862–2871.
16. YoungbloodB, WherryEJ, AhmedR (2011) Acquired transcriptional programming in functional and exhausted virus-specific CD8 T cells. Curr Opin HIV AIDS 7: 50–57.
17. DayCL, KaufmannDE, KiepielaP, BrownJA, MoodleyES, et al. (2006) PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443: 350–354.
18. JacobsonJG, LeibDA, GoldsteinDJ, BogardCL, SchafferPA, et al. (1989) A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive acute and reactivatable latent infections of mice and for replication in mouse cells. Virology 173: 276–283.
19. HeinemanTC, CohenJI (1994) Deletion of the varicella-zoster virus large subunit of ribonucleotide reductase impairs growth of virus in vitro. Journal of Virology 68: 3317–3323.
20. LaingKJ, DongL, SidneyJ, SetteA, KoelleDM (2012) Immunology in the Clinic Review Series; focus on host responses: T cell responses to herpes simplex viruses. Clinical & Experimental Immunology 167: 47–58.
21. JingL, HaasJ, ChongTM, BrucknerJJ, DannGC, et al. (2012) Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. Journal of Clinical Investigation 122: 654–673.
22. PosavadCM, WaldA, HoskenN, HuangML, KoelleDM, et al. (2003) T Cell Immunity to Herpes Simplex Viruses in Seronegative Subjects: Silent Infection or Acquired Immunity? J Immunol 170: 4380–4388.
23. RessingME, HorstD, GriffinBD, TellamJ, ZuoJ, et al. (2008) Epstein-Barr virus evasion of CD8+ and CD4+ T cell immunity via concerted actions of multiple gene products. Seminars in Cancer Biology 18: 397–408.
24. SchifferJT, CoreyL (2013) Rapid host immune response and viral dynamics in herpes simplex virus-2 infection. Nat Med 19: 280–288.
25. ZajacAJ, BlattmanJN, Murali-KrishnaK, SourdiveDJ, SureshM, et al. (1998) Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188: 2205–2213.
26. BarberDL, WherryEJ, MasopustD, ZhuB, AllisonJP, et al. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682–687.
27. MasopustD, HaS-J, VezysV, AhmedR (2006) Stimulation History Dictates Memory CD8 T Cell Phenotype: Implications for Prime-Boost Vaccination. J Immunol 177: 831–839.
28. QuinlivanM, BreuerJ, SchmidDS (2011) Molecular studies of the Oka varicella vaccine. Expert Review of Vaccines 10: 1321–1336.
29. HillA, JugovicP, YorkI, RussG, BenninkJ, et al. (1995) Herpes simplex virus turns off the TAP to evade host immunity. Nature 375: 411–415.
30. HislopAD, RessingME, van LeeuwenD, PudneyVA, HorstD, et al. (2007) A CD8+ T cell immune evasion protein specific to Epstein-Barr virus and its close relatives in Old World primates. J Exp Med 204: 1863–1873.
31. AbendrothA, KinchingtonPR, SlobedmanB (2010) Varicella Zoster Virus Immune Evasion Strategies. Curr Top Microbiol Immunol 342: 155–71.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2014 Číslo 3
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- Cytomegalovirus m154 Hinders CD48 Cell-Surface Expression and Promotes Viral Escape from Host Natural Killer Cell Control
- Human African Trypanosomiasis and Immunological Memory: Effect on Phenotypic Lymphocyte Profiles and Humoral Immunity
- Conflicting Interests in the Pathogen–Host Tug of War: Fungal Micronutrient Scavenging Versus Mammalian Nutritional Immunity
- DHX36 Enhances RIG-I Signaling by Facilitating PKR-Mediated Antiviral Stress Granule Formation