Combinations of Two Capsid Regions Controlling Canine Host Range Determine Canine Transferrin Receptor Binding by Canine and Feline Parvoviruses

James A. Baker Institute, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Journal of Virology (Impact Factor: 4.44). 10/2003; 77(18):10099-105. DOI: 10.1128/JVI.77.18.10099-10105.2003
Source: PubMed


Feline panleukopenia virus (FPV) and its host range variant, canine parvovirus (CPV), can bind the feline transferrin receptor (TfR), while only CPV binds to the canine TfR. Introducing two CPV-specific changes into FPV (at VP2 residues 93 and 323) endowed that virus with the canine TfR binding property and allowed canine cell infection, although neither change alone altered either property. In CPV the reciprocal changes of VP2 residue 93 or 323 to the FPV sequences individually resulted in modest reductions in infectivity for canine cells. Changing both residues in CPV to the FPV amino acids blocked the canine cell infection, but that virus was still able to bind the canine TfR at low levels. This shows that both CPV-specific changes control canine TfR binding but that binding is not always sufficient to mediate infection.

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    • "Hoelzer et al. (2008) predicted that 324 residue is under positive selection and is arising independently in different geographic locations. The residue 324 is adjacent to residue 323 which affects canine Transferrin Receptor (TfR) binding along with residue 93 (Hafenstein et al., 2007; Hueffer et al., 2003). The 324 mutation is likely to have an effect on CPV host range also. "
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    ABSTRACT: Canine Parvovirus-2 (CPV-2), which emerged in 1978, is considered as the major viral enteric pathogen of the canine population. With the emergence of new antigenic variants and incidences of vaccine failure, CPV has become one of the dreaded diseases of the canines worldwide. The present study was undertaken in an organized kennel from North India to ascertain the molecular basis of the CPV outbreaks in the vaccinated dogs. 415 samples were collected over a five year period (2008-2012). The outbreak of the disease was more severe in 2012 with high incidence of mortality in pups with pronounced clinical symptoms. Molecular typing based on the VP2 gene was carried out with the 11 isolates from different years and compared with the CPV prototype and the vaccine strains. All the isolates in the study were either new CPV-2a (2012 isolates) or new CPV-2b (2008 and 2011 isolates). There were amino acid mutations at the Tyr324Ile and at the Thr440Ala position in five isolates from 2012 indicating new CPV mutants spreading in India. The CPV vaccines used in the present study failed to generate protective antibody titer against heterogeneous CPV antigenic types. The findings were confirmed when the affected pups were treated with hyper-immune heterogeneous purified immunoglobulin's against CPV in dogs of different antigenic types.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 01/2014; 23. DOI:10.1016/j.meegid.2014.01.015 · 3.02 Impact Factor
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    • "VP2 (426 amino acid residues) is the main component in CPV capsid which possesses strong antigenic properties. The canine transferrin receptor (TfR) has been identified as a receptor for CPV infection mediated by VP2-TfR interaction [5–7]. "
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    ABSTRACT: Canine parvovirus (CPV) disease is an acute, highly infectious disease threatening the dog-raising industry. So far there are no effective therapeutic strategies to control this disease. Although the canine transferrin receptor (TfR) was identified as a receptor for CPV infection, whether extracellular domain of TfR (called soluble TfR (sTfR)) possesses anti-CPV activities remains elusive. Here, we used the recombinant sTfR prepared from HEK293T cells with codon-optimized gene structure to investigate its anti-CPV activity both in vitro and in vivo. Our results indicated that codon optimization could significantly improve sTfR expression in HEK293T cells. The prepared recombinant sTfR possessed a binding activity to both CPV and CPV VP2 capsid proteins and significantly inhibited CPV infection of cultured feline F81 cells and decreased the mortality of CPV-infected dogs, which indicates that the sTfR has the anti-CPV activity both in vitro and in vivo.
    09/2013; 2013:172479. DOI:10.1155/2013/172479
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    • "The canine and feline host ranges of CPV and FPV appear to be controlled primarily by residues in the viral capsid. The ability of CPV to bind the canine TfR and infect canine cells is largely controlled by mutations of VP2 residues 93 (Lys to Asn) and 323 (Asp to Asn) in the viral capsid, which together determine the canine host range of CPV [29, 30, 55] (Fig. 1). The mutations in CPV-2 which affect the ability to infect and replicate in cats have been less clearly defined, but at least two regions in the capsid protein gene, and in particular substitutions of VP2 residues 87, 300 and 305 appear to be involved [55]. "
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    ABSTRACT: The emergence of canine parvovirus (CPV) represents a well-documented example highlighting the emergence of a new virus through cross-species transmission. CPV emerged in the mid-1970s as a new pathogen of dogs and has since become endemic in the global dog population. Despite widespread vaccination, CPV has remained a widespread disease of dogs, and new genetic and antigenic variants have arisen and sometimes reached high frequency in certain geographic regions or throughout the world. Here we review our understanding of this emergence event and contrast it to what is known about the emergence of a disease in mink caused by mink enteritis virus (MEV). In addition, we summarize the evolution of CPV over the past 30 years in the global dog population, and describe the epidemiology of contemporary parvovirus infections of dogs and cats. CPV represents a valuable model for understanding disease emergence through cross-species transmission, while MEV provides an interesting comparison.
    Veterinary Research 02/2010; 41(6):39. DOI:10.1051/vetres/2010011 · 2.82 Impact Factor
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