Attenuation of chicken anemia virus by site-directed mutagenesis of VP2 Free

Abstract

Chicken anemia virus (CAV) is a significant immunosuppressive pathogen of chickens, but relatively little is known about the effect of specific mutations on its virulence. In order to study the virulence of CAV, an infection model was developed in embryos. Significant growth depression, measured as a reduction in mean body weight, was found for wild-type CAV infection. Infection with wild-type CAV resulted in a significant reduction in thymic and splenic weights and consistently produced severe lesions in the thymus, spleen and bone marrow, as well as haemorrhages. CAVs mutated in the VP2 gene were infectious for embryos, but were highly attenuated with respect to growth depression and CAV-specific pathology. Relative to wild-type infection, viruses Mut C86R, Mut R101G, Mut H103Y, Mut R129G, Mut Q131P, Mut R/K/K150/151/152G/A/A, Mut D/E161/162G/G and Mut E186G were highly attenuated, and viruses Mut L163P and Mut D169G were moderately attenuated. Attenuation of the ability to produce lesions was found consistently for the thymus, spleen and bone marrow, thymic and splenic weights, and for CAV-induced haemorrhage. There was no growth depression associated with infection by the group of highly attenuated mutant viruses and a moderate reduction in mean body weight was only found for virus Mut L163P. These findings show that mutations in the VP2 gene can reduce the virulence of CAV and these mutant viruses may have value as vaccine candidates.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82904-0
2007-08-01
2024-03-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/88/8/2168.html?itemId=/content/journal/jgv/10.1099/vir.0.82904-0&mimeType=html&fmt=ahah

References

  1. Brown H. K., Browning G. F., Scott P. C., Crabb B. S. 2000; Full-length infectious clone of a pathogenic Australian isolate of chicken anaemia virus. Aust Vet J 78:637–640 [CrossRef]
    [Google Scholar]
  2. Büchen-Osmond C. 2006 ICTVdB Management (2006 00.016.0.02. Gyrovirus. In ICTVdB – The Universal Virus Database, version 4 Columbia University; New York, USA:
    [Google Scholar]
  3. Connor T. J., McNeilly F., Firth G. A., McNulty M. S. 1991; Biological characterisation of Australian isolates of chicken anaemia agent. Aust Vet J 68:199–201 [CrossRef]
    [Google Scholar]
  4. Danen-Van Oorschot A. A., Fischer D. F., Grimbergen J. M., Klein B., Zhuang S., Falkenburg J. H., Backendorf C., Quax P. H., Van der Eb A. J., Noteborn M. H. 1997; Apoptin induces apoptosis in human transformed and malignant cells but not in normal cells. Proc Natl Acad Sci U S A 94:5843–5847 [CrossRef]
    [Google Scholar]
  5. Danen-Van Oorschot A. A., van der Eb A. J., Noteborn M. H. 1999; BCL-2 stimulates apoptin-induced apoptosis. Adv Exp Med Biol 457:245–249
    [Google Scholar]
  6. Danen-Van Oorschot A. A., van Der Eb A. J., Noteborn M. H. 2000; The chicken anemia virus-derived protein apoptin requires activation of caspases for induction of apoptosis in human tumor cells. J Virol 74:7072–7078 [CrossRef]
    [Google Scholar]
  7. Engstrom B., Fossum O., Luthman M. 1988; Blue wing disease of chickens: experimental infection with a Swedish isolate of chicken anaemia agent and avian reovirus. Avian Pathol 17:33–50 [CrossRef]
    [Google Scholar]
  8. Farkas T., Tanaka A., Kai K., Kanoe M. 1996; Cloning and sequencing of the genome of chicken anaemia virus (CAV) TK-5803 strain and comparison with other CAV strains. J Vet Med Sci 58:681–684 [CrossRef]
    [Google Scholar]
  9. Goryo M., Suwa T., Matsumoto S., Umemura T., Itakura C. 1987; Serial propagation and purification of chicken anaemia agent in MDCC-MSB1 cell line. Avian Pathol 16:149–163 [CrossRef]
    [Google Scholar]
  10. Goryo M., Suwa T., Umemura T., Itakura C., Yamashiro S. 1989; Histopathology of chicks inoculated with chicken anaemia agent (MSB1–TK5803 strain). Avian Pathol 18:73–89 [CrossRef]
    [Google Scholar]
  11. Imai K., Mase M., Tsukamoto K., Hihara H., Yuasa N. 1999; Persistent infection with chicken anaemia virus and some effects of highly virulent infectious bursal disease virus infection on its persistency. Res Vet Sci 67:233–238 [CrossRef]
    [Google Scholar]
  12. Lamichhane C. M., Snyder D. B., Goodwin M. A., Mengel S. A., Brown J., Dickson T. G. 1991; Pathogenicity of CL-1 chicken anemia agent. Avian Dis 35:515–522 [CrossRef]
    [Google Scholar]
  13. McNulty M. S. 1991; Chicken anaemia agent: a review. Avian Pathol 20:187–203 [CrossRef]
    [Google Scholar]
  14. McNulty M. S., Connor T. J., McNeilly F., Spackman D. 1989; Chicken anemia agent in the United States: isolation of the virus and detection of antibody in broiler breeder flocks. Avian Dis 33:691–694 [CrossRef]
    [Google Scholar]
  15. McNulty M. S., Mackie D. P., Pollock D. A., McNair J., Todd D., Mawhinney K. A., Connor T. J., McNeilly F. 1990; Production and preliminary characterisation of monoclonal antibodies to chicken anemia agent. Avian Dis 34:352–358 [CrossRef]
    [Google Scholar]
  16. Peters M. A., Jackson D. C., Crabb B. S., Browning G. F. 2005; Mutation of chicken anemia virus VP2 differentially affects serine/threonine and tyrosine protein phosphatase activities. J Gen Virol 86:623–630 [CrossRef]
    [Google Scholar]
  17. Peters M. A., Crabb B. S., Washington E. A., Browning G. F. 2006; Site-directed mutagenesis of the VP2 gene of chicken anemia virus affects virus replication, cytopathology and host-cell MHC class I expression. J Gen Virol 87:823–831 [CrossRef]
    [Google Scholar]
  18. Pringle C. R. 1999; Virus taxonomy at the XIth International Congress of Virology. Sydney, Australia: 1999 Arch Virol 144:2065–2070 [CrossRef]
    [Google Scholar]
  19. Rosenberger J. K., Cloud S. S. 1989; The effects of age, route of exposure, and coinfection with infectious bursal disease virus on the pathogenicity and transmissibility of chicken anemia agent (CAA). Avian Dis 33:753–759 [CrossRef]
    [Google Scholar]
  20. Stanislawek W. L., Howell J. 1994; Isolation of chicken anemia virus from broiler chickens in New Zealand. N Z Vet J 42:58–62 [CrossRef]
    [Google Scholar]
  21. Taniguchi T., Yuasa N., Maeda M., Horiuchi T. 1982; Haematological changes in dead and moribund chicks induced by chicken anemia agent. Natl Inst Anim Health Q (Tokyo 22:61–69
    [Google Scholar]
  22. Todd D., Creelan J. L., Mackie D. P., Rixon F., McNulty M. S. 1990; Purification and biochemical characterization of chicken anaemia agent. J Gen Virol 71:819–823 [CrossRef]
    [Google Scholar]
  23. von Bulow V., Fuchs B. 1986; Properties of the causative agent of avian infectious anaemia (chicken anaemia agent, CAA) in vitro . Dtsch Tierarztl Wochenschr 93:9–11
    [Google Scholar]
  24. Yuasa N., Taniguchi T., Imada T., Hihara H. 1983; Distribution of chicken anemia agent (CAA) and detection of neutralizing antibody in chicks experimentally inoculated with CAA. Natl Inst Anim Health Q (Tokyo) 23:78–81
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82904-0
Loading
/content/journal/jgv/10.1099/vir.0.82904-0
Loading

Data & Media loading...

Most cited Most Cited RSS feed