1887

Abstract

The γ-herpesviruses have proved hard to vaccination against, with no convincing protection against long-term latent infection by recombinant viral subunits. In experimental settings, whole-virus vaccines have proved more effective, even when the vaccine virus itself establishes latent infection poorly. The main alternative is replication-deficient virus particles. Here high-dose, replication-deficient murid herpesvirus-4 only protected mice partially against wild-type infection. By contrast, latency-deficient but replication-competent vaccine protected mice strongly, even when delivered non-invasively to the olfactory epithelium. Thus, this approach seems to provide the best chance of a safe and effective γ-herpesvirus vaccine.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001391
2020-01-27
2020-02-28
Loading full text...

Full text loading...

References

  1. Cohen JI, Mocarski ES, Raab-Traub N, Corey L, Nabel GJ. The need and challenges for development of an Epstein-Barr virus vaccine. Vaccine 2013;31:B194–B196 [CrossRef]
    [Google Scholar]
  2. Young LS, Finerty S, Brooks L, Scullion F, Rickinson AB et al. Epstein-Barr virus gene expression in malignant lymphomas induced by experimental virus infection of cottontop tamarins. J Virol 1989;63:1967–1974 [CrossRef]
    [Google Scholar]
  3. Thorley-Lawson DA, Hawkins JB, Tracy SI, Shapiro M. The pathogenesis of Epstein-Barr virus persistent infection. Curr Opin Virol 2013;3:227–232 [CrossRef]
    [Google Scholar]
  4. Barton E, Mandal P, Speck SH. Pathogenesis and host control of gammaherpesviruses: lessons from the mouse. Annu Rev Immunol 2011;29:351–397 [CrossRef]
    [Google Scholar]
  5. Gaspar M, May JS, Sukla S, Frederico B, Gill MB et al. Murid herpesvirus-4 exploits dendritic cells to infect B cells. PLoS Pathog 2011;7:e1002346 [CrossRef]
    [Google Scholar]
  6. Bridgeman A, Stevenson PG, Simas JP, Efstathiou S. A secreted chemokine binding protein encoded by murine gammaherpesvirus-68 is necessary for the establishment of a normal latent load. J Exp Med 2001;194:301–312 [CrossRef]
    [Google Scholar]
  7. Rice J, de Lima B, Stevenson FK, Stevenson PG. A gamma-herpesvirus immune evasion gene allows tumor cells in vivo to escape attack by cytotoxic T cells specific for a tumor epitope. Eur J Immunol 2002;32:3481–3487 [CrossRef]
    [Google Scholar]
  8. Stevenson PG, Simas JP, Efstathiou S. Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4. J Gen Virol 2009;90:2317–2330 [CrossRef]
    [Google Scholar]
  9. van Zyl DG, Tsai M-H, Shumilov A, Schneidt V, Poirey R et al. Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. PLoS Pathog 2018;14:e1007464 [CrossRef]
    [Google Scholar]
  10. Münz C. Human γ-herpesvirus infection, tumorigenesis, and immune control in mice with reconstituted human immune system components. Front Immunol 2018;9:238 [CrossRef]
    [Google Scholar]
  11. Babcock GJ, Decker LL, Freeman RB, Thorley-Lawson DA. Epstein-Barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients. J Exp Med 1999;190:567–576 [CrossRef]
    [Google Scholar]
  12. Farrell PJ. Epstein-Barr virus strain variation. Curr Top Microbiol Immunol 2015;390:45–69 [CrossRef]
    [Google Scholar]
  13. Gadola SD, Moins-Teisserenc HT, Trowsdale J, Gross WL, Cerundolo V. Tap deficiency syndrome. Clin Exp Immunol 2000;121:173–178 [CrossRef]
    [Google Scholar]
  14. de la Salle H, Houssaint E, Peyrat MA, Arnold D, Salamero J et al. Human peptide transporter deficiency: importance of HLA-B in the presentation of TAP-independent EBV antigens. J Immunol 1997;158:4555–4563
    [Google Scholar]
  15. Moser JM, Farrell ML, Krug LT, Upton JW, Speck SH. A gammaherpesvirus 68 gene 50 null mutant establishes long-term latency in the lung but fails to vaccinate against a wild-type virus challenge. J Virol 2006;80:1592–1598 [CrossRef]
    [Google Scholar]
  16. Lawler C, Milho R, May JS, Stevenson PG. Rhadinovirus host entry by co-operative infection. PLoS Pathog 2015;11:e1004761 [CrossRef]
    [Google Scholar]
  17. Milho R, Frederico B, Efstathiou S, Stevenson PG. A heparan-dependent herpesvirus targets the olfactory neuroepithelium for host entry. PLoS Pathog 2012;8:e1002986 [CrossRef]
    [Google Scholar]
  18. Fowler P, Marques S, Simas JP, Efstathiou S. ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J Gen Virol 2003;84:3405–3416 [CrossRef]
    [Google Scholar]
  19. Stevenson PG, May JS, Connor V, Efstathiou S. Vaccination against a Hit-and-run viral cancer. J Gen Virol 2010;91:2176–2185 [CrossRef]
    [Google Scholar]
  20. Milho R, Smith CM, Marques S, Alenquer M, May JS et al. In vivo imaging of murid herpesvirus-4 infection. J Gen Virol 2009;90:21–32 [CrossRef]
    [Google Scholar]
  21. Aricò E, Robertson KA, Belardelli F, Ferrantini M, Nash AA. Vaccination with inactivated murine gammaherpesvirus 68 strongly limits viral replication and latency and protects type I IFN receptor knockout mice from a lethal infection. Vaccine 2004;22:1433–1440 [CrossRef]
    [Google Scholar]
  22. Stevenson PG, Belz GT, Castrucci MR, Altman JD, Doherty PC. A gamma-herpesvirus sneaks through a CD8(+) T cell response primed to a lytic-phase epitope. Proc Natl Acad Sci U S A 1999;96:9281–9286 [CrossRef]
    [Google Scholar]
  23. Glauser DL, Milho R, Lawler C, Stevenson PG. Antibody arrests γ-herpesvirus olfactory super-infection independently of neutralization. J Gen Virol 2019;100:246–258 [CrossRef]
    [Google Scholar]
  24. Stevenson PG. Immune Control of γ-Herpesviruses. Viral Immunol 2019; [CrossRef]
    [Google Scholar]
  25. Lawler C, Simas JP, Stevenson PG. Vaccine protection against murid herpesvirus-4 is maintained when the priming virus lacks known latency genes. Immunol Cell Biol 2020;98:67-7867–78 [CrossRef]
    [Google Scholar]
  26. Palmeira L, Sorel O, Van Campe W, Boudry C, Roels S et al. An essential role for γ-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle. Proc Natl Acad Sci U S A 2013;110:E1933–E1942 [CrossRef]
    [Google Scholar]
  27. Shivkumar M, Milho R, May JS, Nicoll MP, Efstathiou S et al. Herpes simplex virus 1 targets the murine olfactory neuroepithelium for host entry. J Virol 2013;87:10477–10488 [CrossRef]
    [Google Scholar]
  28. Farrell HE, Lawler C, Tan CSE, MacDonald K, Bruce K et al. Murine cytomegalovirus exploits olfaction to enter new hosts. mBio 2016;7:e00251 [CrossRef]
    [Google Scholar]
  29. E X, Meraner P, Lu P, Perreira JM, Aker AM et al. OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism. Proc Natl Acad Sci U S A 2019;116:7043–7052 [CrossRef]
    [Google Scholar]
  30. Okuno K, Takashima K, Kanai K, Ohashi M, Hyuga R et al. Epstein-Barr virus can infect rabbits by the intranasal or peroral route: an animal model for natural primary EBV infection in humans. J Med Virol 2010;82:977–986 [CrossRef]
    [Google Scholar]
  31. Dunmire SK, Grimm JM, Schmeling DO, Balfour HH, Hogquist KA. The incubation period of primary Epstein-Barr virus infection: viral dynamics and immunologic events. PLoS Pathog 2015;11:e1005286 [CrossRef]
    [Google Scholar]
  32. Tan CSE, Stevenson PG. B cell response to herpesvirus infection of the olfactory neuroepithelium. J Virol 2014;88:14030–14039 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001391
Loading
/content/journal/jgv/10.1099/jgv.0.001391
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error