1887

Abstract

Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell–Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation , and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000936
2017-11-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/98/11/2759.html?itemId=/content/journal/jgv/10.1099/jgv.0.000936&mimeType=html&fmt=ahah

References

  1. McCaw DL, Hoskins JD. Canine viral enteritis. In Greene CE. (editor) Infectious Disease of the Dog and Cat, 3rd ed. St. Louis, MO: Saunders Elsevier; 2006 pp. 63–73
    [Google Scholar]
  2. Cotmore SF, Agbandje-Mckenna M, Chiorini JA, Mukha DV, Pintel DJ et al. The family Parvoviridae . Arch Virol 2014; 159:1239–1247 [View Article][PubMed]
    [Google Scholar]
  3. Reed AP, Jones EV, Miller TJ. Nucleotide sequence and genome organization of canine parvovirus. J Virol 1988; 62:266–276[PubMed]
    [Google Scholar]
  4. Jongeneel CV, Sahli R, Mcmaster GK, Hirt B. A precise map of splice junctions in the mRNAs of minute virus of mice, an autonomous parvovirus. J Virol 1986; 59:564–573[PubMed]
    [Google Scholar]
  5. Parrish CR. Structures and functions of parvovirus capsids and the process of cell infection. Curr Top Microbiol Immunol 2010; 343:149–176 [View Article][PubMed]
    [Google Scholar]
  6. Weichert WS, Parker JS, Wahid AT, Chang SF, Meier E et al. Assaying for structural variation in the parvovirus capsid and its role in infection. Virology 1998; 250:106–117 [View Article][PubMed]
    [Google Scholar]
  7. Allison AB, Kohler DJ, Ortega A, Hoover EA, Grove DM et al. Host-specific parvovirus evolution in nature is recapitulated by in vitro adaptation to different carnivore species. PLoS Pathog 2014; 10:e1004475 [View Article][PubMed]
    [Google Scholar]
  8. Hueffer K, Govindasamy L, Agbandje-Mckenna M, Parrish CR. Combinations of two capsid regions controlling canine host range determine canine transferrin receptor binding by canine and feline parvoviruses. J Virol 2003; 77:10099–10105 [View Article][PubMed]
    [Google Scholar]
  9. Kailasan S, Agbandje-Mckenna M, Parrish CR. Parvovirus family conundrum: what makes a killer?. Annu Rev Virol 2015; 2:425–450 [View Article][PubMed]
    [Google Scholar]
  10. Stevenson MA, Fox JM, Wolfinbarger JB, Bloom ME. Effect of a valine residue at codon 352 of the VP2 capsid protein on in vivo replication and pathogenesis of Aleutian disease parvovirus in mink. Am J Vet Res 2001; 62:1658–1663 [View Article][PubMed]
    [Google Scholar]
  11. Decaro N, Buonavoglia C. Canine parvovirus-a review of epidemiological and diagnostic aspects, with emphasis on type 2c. Vet Microbiol 2012; 155:1–12 [View Article][PubMed]
    [Google Scholar]
  12. Zhou P, Zeng W, Zhang X, Li S. The genetic evolution of canine parvovirus - A new perspective. PLoS One 2017; 12:3 [View Article][PubMed]
    [Google Scholar]
  13. Bass EP, Gill MA, Beckenhauer WH. Development of a modified live, canine origin parvovirus vaccine. J Am Vet Med Assoc 1982; 181:909–913[PubMed]
    [Google Scholar]
  14. Churchill AE. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin. Vet Rec 1987; 120:334–339 [View Article][PubMed]
    [Google Scholar]
  15. Wilson S, Stirling C, Borowski S, Thomas A, King V et al. Vaccination of dogs with duramune DAPPi+LC protects against pathogenic canine parvovirus type 2c challenge. Vet Rec 2013; 172:662 [View Article][PubMed]
    [Google Scholar]
  16. Badgett MR, Auer A, Carmichael LE, Parrish CR, Bull JJ. Evolutionary dynamics of viral attenuation. J Virol 2002; 76:10524–10529 [View Article][PubMed]
    [Google Scholar]
  17. Decaro N, Desario C, Elia G, Campolo M, Lorusso A et al. Occurrence of severe gastroenteritis in pups after canine parvovirus vaccine administration: a clinical and laboratory diagnostic dilemma. Vaccine 2007; 25:1161–1166 [View Article][PubMed]
    [Google Scholar]
  18. Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC et al. Asymmetric binding of transferrin receptor to parvovirus capsids. Proc Natl Acad Sci USA 2007; 104:6585–6589 [View Article][PubMed]
    [Google Scholar]
  19. Strassheim ML, Gruenberg A, Veijalainen P, Sgro JY, Parrish CR. Two dominant neutralizing antigenic determinants of canine parvovirus are found on the threefold spike of the virus capsid. Virology 1994; 198:175–184 [View Article][PubMed]
    [Google Scholar]
  20. Allison AB, Organtini LJ, Zhang S, Hafenstein SL, Holmes EC et al. Single mutations in the VP2 300 loop region of the three-fold spike of the carnivore parvovirus capsid can determine host range. J Virol 2015; 90:753–767 [View Article][PubMed]
    [Google Scholar]
  21. Parker JS, Parrish CR. Canine parvovirus host range is determined by the specific conformation of an additional region of the capsid. J Virol 1997; 71:9214–9222[PubMed]
    [Google Scholar]
  22. Meunier PC, Cooper BJ, Appel MJ, Slauson DO. Pathogenesis of canine parvovirus enteritis: the importance of viremia. Vet Pathol 1985; 22:60–71 [View Article][PubMed]
    [Google Scholar]
  23. Nho WG, Sur JH, Doster AR, Kim SB. Detection of canine parvovirus in naturally infected dogs with enteritis and myocarditis by in situ hybridization. J Vet Diagn Invest 1997; 9:255–260 [View Article][PubMed]
    [Google Scholar]
  24. Simpson AA, Chandrasekar V, Hébert B, Sullivan GM, Rossmann MG et al. Host range and variability of calcium binding by surface loops in the capsids of canine and feline parvoviruses. J Mol Biol 2000; 300:597–610 [View Article][PubMed]
    [Google Scholar]
  25. Tsao J, Chapman MS, Agbandje M, Keller W, Smith K et al. The three-dimensional structure of canine parvovirus and its functional implications. Science 1991; 251:1456–1464 [View Article][PubMed]
    [Google Scholar]
  26. Govindasamy L, Hueffer K, Parrish CR, Agbandje-Mckenna M. Structures of host range-controlling regions of the capsids of canine and feline parvoviruses and mutants. J Virol 2003; 77:12211–12221 [View Article][PubMed]
    [Google Scholar]
  27. Truyen U, Evermann JF, Vieler E, Parrish CR. Evolution of canine parvovirus involved loss and gain of feline host range. Virology 1996; 215:186–189 [View Article][PubMed]
    [Google Scholar]
  28. Ben Abdeljelil N, Khabouchi N, Kassar S, Miled K, Boubaker S et al. Simultaneous alteration of residues 279 and 284 of the VP2 major capsid protein of a very virulent Infectious Bursal Disease Virus (vvIBDV) strain did not lead to attenuation in chickens. Virol J 2014; 11:199 [View Article][PubMed]
    [Google Scholar]
  29. Chen Y, Lu Z, Zhang L, Gao L, Wang N et al. Ribosomal protein L4 interacts with viral protein VP3 and regulates the replication of infectious bursal disease virus. Virus Res 2016; 211:73–78 [View Article][PubMed]
    [Google Scholar]
  30. Zhang L, Ren X, Chen Y, Gao Y, Wang N et al. Chondroitin sulfate N-acetylgalactosaminyltransferase-2 contributes to the replication of infectious bursal disease virus via interaction with the capsid protein VP2. Viruses 2015; 7:1474–1491 [View Article][PubMed]
    [Google Scholar]
  31. Tu M, Liu F, Chen S, Wang M, Cheng A. Role of capsid proteins in parvoviruses infection. Virol J 2015; 12:114 [View Article][PubMed]
    [Google Scholar]
  32. Horiuchi M, Shinagawa M. Construction of an infectious DNA clone of the Y1 strain of canine parvovirus and characterization of the virus derived from the clone. Arch Virol 1993; 130:227–236 [View Article][PubMed]
    [Google Scholar]
  33. Sambrook J, Russell DW. Molecular Cloning, 3rd ed. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory; 2001 pp. 1.31–1.162
    [Google Scholar]
  34. Burleson FG, Chambers TM, Wiedbrauk DL. Virus quantification. Virology: A Laboratory Manual San Diego, CA: Academic Press; 1992 pp. 53–97
    [Google Scholar]
  35. Nakamura K, Sakamoto M, Ikeda Y, Sato E, Kawakami K et al. Pathogenic potential of canine parvovirus types 2a and 2c in domestic cats. Clin Diagn Lab Immunol 2001; 8:663–668 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000936
Loading
/content/journal/jgv/10.1099/jgv.0.000936
Loading

Data & Media loading...

Supplements

Supplementary File 1

PDF
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