Source: CORNELL UNIVERSITY submitted to NRP
STRAIN VARIATION IN CANINE PARVOVIRUS
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
EXTENDED
Funding Source
Reporting Frequency
Annual
Accession No.
0137241
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Jan 1, 1989
Project End Date
Dec 31, 2009
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
CORNELL UNIVERSITY
(N/A)
ITHACA,NY 14853
Performing Department
JAMES A. BAKER INSTITUTE FOR ANIMAL HEALTH
Non Technical Summary
(N/A)
Animal Health Component
(N/A)
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3113899104034%
3113899103033%
3113899110133%
Goals / Objectives
Analyze and compare 2 variant strains of canine parvovirus. Map sequence differences determining antigenic epitopes. Examine for differences in virulence or replication in dogs. Compare the antigenic crossreactivities in neutralization tests.
Project Methods
Rearrangements of cloned DNA containing the viral capsid protein genes expressedin a bovine papilloma virus vector would be used to produce empty parvovirus capsids. Those would be examined for the antigenic types and other properties of the two parvovirus types. Animal infections by each virus type would be compared to reveal any epidemiological advantages of one virus type over the others.

Progress 01/01/92 to 12/31/92

Outputs
Since emerging in 1978, canine parvovirus (CPV) has undergone variation in antigenic type and a parallel variation in sequence. The first of the new antigenic types of virus (which we called CPV-2a) apparently arose in parallel with the original CPV, and replaced the first-recognized virus during 1979 and 1980, and most recently we showed that a further change had occurred during the mid-1980s, with replacement of the CPV type-2a strain by the CPV type-2b (Parrish et al., 1991). The global replacement of the first virus type by the second, and the subsequent replacement of the second by the third are highly unusual events, and appear most similar to the antigenic drift of influenza virus in humans. Our collaboration with a several workers at Purdue University, has lead most recently to the solving of the atomic structure of feline panleukopenia virus (FPV) empty capsids (Agbandje et al., 1993). Comparing the structures of CPV and FPV has shed much light on the locations and features of the sequence differences between the two viruses - the sequence differences which affect canine host range in CPV were seen to be on the surface of the capsid, at interfaces between the VP2 monomers (Change et al., 1992). Sequences which affect feline host range (residues 80, 564 and 568) apparently were observed to cause changes in the intermolecular contacts between VP2 monomers, at a position where 3 amino acid chains interact around the fivefold contacts.

Impacts
(N/A)

Publications

  • SALIKI, J., MIZAK, B., FLORE, H., GETTIG, R., BURAND, J., CARMICHAEL, L.E., WOOD, H. A., PARRISH, C.R. (1992). Canine parvovirus empty capsids produced by expression in a baculovirus vector - use in analysis of viral properties and immun.
  • TRUYEN, U. and PARRISH, C.R. (1992) The canine and feline host ranges of canine parvovirus and feline panleukopenia virus: distinct host cell tropisms of each virus in vitro and in vivo. J. Virol. 66:5399-5408.
  • BARBIS, D. P., CHANG, S-F., and PARRISH, C.R. (1992) Mutations adjacent to the dimple of the canine parvovirus capsid s structure affect sialic acid binding. Virology 191:301-308.
  • CHANG, S-F., SGRO, J-Y., and PARRISH, C.R. (1992). Multiple amino acids in the capsid structure of canine parvovirus coordinately determine the canine host range and specific antigenic and hemagglutination properties. J. Virol. 66:6858-.
  • AGBANDJE, J., MCKENNA, R., ROSSMANN, M.G., STRASSHEIM, M. L., PARRISH, C.R. (1993). Structure determination of feline panleukopenia virus empty particles. Proteins, in press.
  • STRASSHEIM, M. L., GRUENBERG, A., VEIJALAINEN, P., SGRO, J-Y., PARRISH, C.R. (1993). Two dominant neutralizing antigenic determinants of Canine Parvovirus are found on the three-fold spike of the virus capsid. Submitted to Virology, M.


Progress 01/01/91 to 12/30/91

Outputs
We have been further analyzing the structure, functions, and variation of canineand feline parvoviruses (CPV and FPV). We have shown that since 1978 the CPV strain infecting dogs in the USA and other countries has changed antigenically on two occasions. The first change occurred around 1980, while the second change occurred around 1984-1986. On both occasions the new strains of virus replaced the previously existing strains in nature. We have defined these changes in detail and show that the viruses have evolved by the accumulation of DNA sequence changes, and that the sequence changes affect both of the defined epitopes on the CPV capsid. This suggests that CPV is undergoing antigenic drift in a manner similar to some influenza virus strains which is an unexpected finding. We are presently examining FPV strains collected over a similar time period to see whether they have also varied in sequence or antigenic type. Other studies have involved the genetic analysis of the differences between those viruses which are encoded within the capsid protein and which result in the ability of the CPV to replicate in dogs. Using site directed mutagenesis of the infectious plasmid clones of the two viruses, we have shown that the ability of the CPV to replicate in dog cells in culture is determined by three coding nucleotide changes in the coat protein gene of the virus. We are continuing to examine the genetic and biological bases of the various host ranges of the viruses.

Impacts
(N/A)

Publications

  • PARRISH, C.R. 1990. The emergence, natural history and variation of canine, mink and feline parvoviruses. Advances in Virus Research 38:404-450.
  • TSAO, J., CHAPMAN, M.S., AGBANDJE, M., KELLER, W., SMITH, K., WU, H., LUO, M., SMITH, T.J., ROSSMANN, M.G., COMPANS, R.W., PARRISH, C.R. 1991. The three-dimensional structure of canine parvovirus and its functional implications.
  • PARRISH, C.R. 1991. Mapping specific functions in the capsid structure of canine parvovirus and feline panleukopenia virus using infectious plasmid clones. Virology 183:195-205.
  • PARRISH, C.R., AQUADRO, C.F., STRASSHEIM, M.L., EVERMANN, J.F., SGRO, J-Y, MOHAMMED, H.O. 1991. Rapid antigenic type replacement and DNA sequence evolution of canine parvovirus. Journal of Virology 65:6544-6552.
  • SALIKI, J.T., MIZAK, B., FLORE, H.P., GETTIG, R.R., BURAND, J.P., CARMICHAEL, L.E., WOOD, H.A. PARRISH, C.R. 1992. Canine parvovirus empty capsids produced by expression in a baculovirus vector-use in analysis of viral properties.


Progress 01/01/89 to 12/30/89

Outputs
We have prepared a complete infectious clone of the original (1978) antigenic type of canine parvovirus (CPV-b), comprising the almost complete genome of the virus (0-98.7 genome map units) in a plasmid vector. That clone is viable after transfection into feline cell cultures, producing a virus indistinguishable from CPV. In other studies we have replaced portions of the CPV-b clone with sequences prepared from the feline panleukopenia virus (FPV) strain-b. The initial clones prepared were transfected into feline cells, and the viruses encoded by those sequences recovered. So far we have prepared several CPV-FPV recombinant viruses, the 64-98.7 m.u. sequence of CPV-d. The virus produced from that recombinant had lost the host range property of CPV, as it did not replicate in canine cells. In addition it had lost the CPV-specific antigenic epitope recognized by certain monoclonal antibodies. Those studies have therefore resulted in the development of a very powerful genetic method for the mapping the host range, antigenic and other biological properties of the parvoviruses of cats and dogs. The information derived during these studies will give a better understanding of the fundamental factors which favor virus variation and emerging viruses. The results obtained will allow us to understand the ways in which, in this case, just a few changes in the base sequence of a virus allowed it to spread around the world, and in the case of CPV-2a completely replacing the previous virus type.

Impacts
(N/A)

Publications

  • NO PUBLICATIONS REPORTED THIS PERIOD.