Pathogenesis of Two Strains of Lion (<i>Panthera leo</i>) Morbillivirus in Ferrets (<i>Mustela putorius furo</i>)

Evermann, James F.; Leathers, C. W.; Gorham, J. R.; McKeirnan, A. J.; Appel, M. J. G.

doi:10.1354/vp.38-3-311

Cited by 29 publications

(32 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It occurs worldwide and produces high morbidity and mortality in immunologically naïve populations (22,29). This virus also infects a broad range of other animals, such as Mustelidae (ferrets, minks, skunks, weasels, and badgers), Procyonidae (raccoons and pandas), Ursidae (bears), Viverridae (civets, genets, and linsangs), hyaenidae (hyenas), and Felidae (lions and tigers) (2,3,4,10,12,16,36). Canine distemper virus is classified in the genus Morbillivirus within the family Paramyxoviridae and has an unsegmented, negative-sense, single-stranded, ϳ15.7-kb RNA genome and an enveloped virus particle that is 150 to 300 nm in diameter (29).…”

mentioning

confidence: 99%

Phylogenetic Characterization of Canine Distemper Viruses Detected in Naturally Infected Dogs in North America

2005

View full text Add to dashboard Cite

In 2004, six puppies and one adult dog from a total of four premises were subjected to necropsy evaluation. For five of the seven dogs, disease caused by canine distemper virus (CDV) infection was suspected based on clinical signs. In all of the dogs, a diagnosis of CDV infection was established by the presence of compatible gross and histologic lesions, immunohistochemical labeling for CDV antigen, and detection of CDV RNA by reverse transcription-PCR. To further characterize the CDV strains detected in the four cases, complete gene sequences were determined for the hemagglutinin (H) and fusion (F) protein genes, while partial gene sequencing was performed for the phosphoprotein gene. A total of 4,508 bases were sequenced for the CDV strains detected from each of the four cases. Two cases were found to have identical sequences except for 2 bases in the intergenic region of the F and H genes. Phylogenetic analysis strongly suggested an evolutionary relationship between sequences detected in these two cases and those of phocine distemper virus 2 and two other strains of CDV not previously detected in the continental United States. Clear phylogenetic relationships were not established for viruses detected in the two additional cases; however, one strain showed similarity to CDV strains detected in a panda from China. Importantly, the three CDV strains detected were demonstrated to be genetically distinct from known vaccine strains and strains previously reported in the continental United States.Canine distemper virus (CDV) is the etiological agent of one the most important viral diseases of wild and domestic Canidae (dog, dingo, fox, coyote, jackal, and wolf) (2). It occurs worldwide and produces high morbidity and mortality in immunologically naïve populations (22,29). This virus also infects a broad range of other animals, such as Mustelidae (ferrets, minks, skunks, weasels, and badgers), Procyonidae (raccoons and pandas), Ursidae (bears), Viverridae (civets, genets, and linsangs), hyaenidae (hyenas), and Felidae (lions and tigers) (2,3,4,10,12,16,36). Canine distemper virus is classified in the genus Morbillivirus within the family Paramyxoviridae and has an unsegmented, negative-sense, single-stranded, ϳ15.7-kb RNA genome and an enveloped virus particle that is 150 to 300 nm in diameter (29). The pathogenesis of CDV infection in dogs has been well characterized (2,22,29,35). The genome of CDV encodes the following virion proteins: matrix (M), fusion (F), hemagglutinin (H), nucleocapsid (N), polymerase (L), and phosphoprotein (P). The H gene protein is responsible for viral attachment to the cell host (38) and may also play a role in induction of protective immunity (11). The H protein is one of the most variable morbillivirus proteins and thus has often been used to assess genetic changes between CDV isolates (8,9,17,18,20,21,23,26,28,30).In this study, postmortem findings, immunohistochemical labeling, and reverse transcription (RT)-PCR specific for CDV genomic RNA established a definitive diagnosis of diseas...

show abstract

mentioning

confidence: 99%

Phylogenetic Characterization of Canine Distemper Viruses Detected in Naturally Infected Dogs in North America

2005

View full text Add to dashboard Cite

show abstract

“…This limitation has led to the development of a range of smallanimal models, which are useful but tend to reflect only limited aspects of the human disease (29,30,33,37,40). These models are augmented by others which use closely related morbilliviruses, such as rinderpest virus (RPV) or canine distemper virus (CDV), to infect natural hosts such as cattle and ferrets (18,49,52). Although many aspects of MV infection of humans are mirrored in the pathogenesis of CDV and RPV, each has its characteristic pattern of disease progression.…”

mentioning

confidence: 99%

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Brown

Rima

Allen

et al. 2005

J Virol

View full text Add to dashboard Cite

Negative-strand RNA viruses encode a single RNA-dependent RNA polymerase (RdRp) which transcribes and replicates the genome. The open reading frame encoding the RdRp from a virulent wild-type strain of rinderpest virus (RPV) was inserted into an expression plasmid. Sequences encoding enhanced green fluorescent protein (EGFP) were inserted into a variable hinge of the RdRp. The resulting polymerase was autofluorescent, and its activity in the replication/transcription of a synthetic minigenome was reduced. We investigated the potential of using this approach to rationally attenuate a virus by inserting the DNA sequences encoding the modified RdRp into a full-length anti-genome plasmid from which a virulent virus (rRPV KO ) can be rescued. A recombinant virus, rRPV KO L-RREGFPR, which grew at an indistinguishable rate and to an identical titer as rRPV KO in vitro, was rescued. Fluorescently tagged polymerase was visible in large cytoplasmic inclusions and beneath the cell membrane. Subcutaneous injection of 10 4 TCID 50 of the rRPV KO parental recombinant virus into cattle leads to severe disease symptoms (leukopenia/diarrhea and pyrexia) and death by 9 days postinfection. Animals infected with rRPV KO L-RREGFPR exhibited transient leukopenia and mild pyrexia, and the only noticeable clinical signs were moderate reddening of one eye and a slight ocular-nasal discharge. Viruses that expressed the modified polymerase were isolated from peripheral blood lymphocytes and eye swabs. This demonstrates that a virulent morbillivirus can be attenuated in a single step solely by modulating RdRp activity and that there is not necessarily a correlation between virus growth in vitro and in vivo.Morbilliviruses cause significant levels of disease in humans and animals throughout the world. For example, the human pathogen measles virus (MV) infects over 40 million individuals per annum and leads to the death of around 800,000 children. The classical course of disease progression is difficult to mimic comprehensively in tractable animal models as the virus has a highly restricted host range. A number of nonhuman primate models have been developed which reproduce many, but not all, aspects of the human disease. However, each has some limitations and they are all dead-end hosts (2,45,47). This limitation has led to the development of a range of smallanimal models, which are useful but tend to reflect only limited aspects of the human disease (29,30,33,37,40). These models are augmented by others which use closely related morbilliviruses, such as rinderpest virus (RPV) or canine distemper virus (CDV), to infect natural hosts such as cattle and ferrets (18, 49, 52). Although many aspects of MV infection of humans are mirrored in the pathogenesis of CDV and RPV, each has its characteristic pattern of disease progression. Thus, wild-type CDV is much more likely to infect the central nervous system than MV, whereas RPV has not been found to infect the central nervous system. In contrast, wild-type RPV has a particular propensity to infec...

show abstract

“…Ferrets are even more susceptible to CDV than dogs, and the lethality of wild-type strains reaches 100% (16,23). When infected with a neurovirulent strain, most ferrets will develop neurological signs that increase with disease progression (4,13).…”

mentioning

confidence: 99%

Disease Duration Determines Canine Distemper Virus Neurovirulence

Bonami

Rudd

Messling

2007

J Virol

View full text Add to dashboard Cite

The Morbillivirus hemagglutinin (H) protein mediates attachment to the target cell. To evaluate its contribution to canine distemper virus neurovirulence, we exchanged the H proteins of the wild-type strains 5804P and A75 and assessed the pathogenesis of the chimeric viruses in ferrets. Both strains are lethal to ferrets; however, 5804P causes a 2-week disease without neurological signs, whereas A75 is associated with a longer disease course and neurological involvement. We observed that both H proteins supported neuroinvasion and the subsequent development of clinical neurological signs if given enough time, demonstrating that disease duration is the main neurovirulence determinant.

show abstract

Pathogenesis of Two Strains of Lion (Panthera leo) Morbillivirus in Ferrets (Mustela putorius furo)

Cited by 29 publications

References 34 publications

Phylogenetic Characterization of Canine Distemper Viruses Detected in Naturally Infected Dogs in North America

Phylogenetic Characterization of Canine Distemper Viruses Detected in Naturally Infected Dogs in North America

Rational Attenuation of a Morbillivirus by Modulating the Activity of the RNA-Dependent RNA Polymerase

Disease Duration Determines Canine Distemper Virus Neurovirulence

Contact Info

Product

Resources

About