These studies will define the relationships between viral structures and functions by examining and genetically mapping differences between the recently emerged canine parvovirus (CPV) and the feline panleukopenia virus (FPV) from which it probably was derived. Infectious genomic clones of the viruses are being prepared, and specific regions of the VP-1/VP-2 gene and other parts of the genomes of FPV, CPV or a host range mutant (CPV-102/10) will be exchanged either before or after in vitro site-directed mutagenesis of defined nucleotides. After transfection of DNA into cell cultures, viruses produced will be examined for host range, for antigenic type with panels of monoclonal antibodies (mAb), or for pH dependence of hemagglutination (HA). In these ways the differences determining the canine and feline host ranges of the viruses and CPV or FPV specific epitopes will be mapped to specific nucleotides and the genetic relationships between the various functions defined. The antigenic structure of the viruses will be determined by sequence analysis of neutralization escape mutants selected with mAb, and by defining the relative efficiencies each epitope in All the functional sequence positions identified within the VP-2 gene will be located within the 3D crystal structure of the CPV capsid, in collaboration with workers at Purdue University. That information will be used to derive a detailed model of the roles of specific structural elements in the functions of these viruses. Restrictive and permissive animal infections would be analyzed by virus isolation, antibody staining for capsid proteins and by strand specific in situ hybridizations for viral or replicative form DNA, or mRNA, defining the in vivo host ranges and the cells which are targets for viral replication. Lymphoid cells in which the viruses replicate in vivo would be cultured in vitro in attempts to develop a culture system which demonstrated the reciprocal host range restriction seen in vivo. The replication of the viruses in permissive and restrictive host cells will be examined to define any specific blocks in the viral replication cycles, or to reveal the actions of cellular factors which permit permissive viral replication. These studies will build on our previous results to provide a detailed molecular model of the mechanisms by which alterations specific parvovirus sequences and structures allow the viruses to vary in host range in animals and in differentiated cells in vitro. In the case of CPV such a variation resulted in the virus gaining the ability to infect the Family Canidae amongst the Canivora, and so these studies are relevant to many important areas of viral biology and human and animal health.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Experimental Virology Study Section (EVR)
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Cornell University
Schools of Veterinary Medicine
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Lyi, Sangbom Michael; Tan, Min Jie Alvin; Parrish, Colin R (2014) Parvovirus particles and movement in the cellular cytoplasm and effects of the cytoskeleton. Virology 456-457:342-52
Löfling, Jonas; Lyi, Sangbom Michael; Parrish, Colin R et al. (2013) Canine and feline parvoviruses preferentially recognize the non-human cell surface sialic acid N-glycolylneuraminic acid. Virology 440:89-96
Allison, Andrew B; Harbison, Carole E; Pagan, Israel et al. (2012) Role of multiple hosts in the cross-species transmission and emergence of a pandemic parvovirus. J Virol 86:865-72
Kaelber, Jason T; Demogines, Ann; Harbison, Carole E et al. (2012) Evolutionary reconstructions of the transferrin receptor of Caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs. PLoS Pathog 8:e1002666
Cureton, David K; Harbison, Carole E; Cocucci, Emanuele et al. (2012) Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures. J Virol 86:5330-40
Flanagan, M L; Parrish, C R; Cobey, S et al. (2012) Anticipating the species jump: surveillance for emerging viral threats. Zoonoses Public Health 59:155-63
Stucker, Karla M; Pagan, Israel; Cifuente, Javier O et al. (2012) The role of evolutionary intermediates in the host adaptation of canine parvovirus. J Virol 86:1514-21
Goodman, Laura B; Lyi, Sangbom M; Johnson, Natalie C et al. (2010) Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection. J Virol 84:4969-78
Hoelzer, Karin; Parrish, Colin R (2010) The emergence of parvoviruses of carnivores. Vet Res 41:39
Harbison, Carole E; Lyi, Sangbom Michael; Weichert, Wendy S et al. (2009) Early steps in cell infection by parvoviruses: host-specific differences in cell receptor binding but similar endosomal trafficking. J Virol 83:10504-14

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