The Ferret in Morbillivirus Research

Messling, Véronika von

doi:10.1002/9781118782699.ch26

Cited by 4 publications

(4 citation statements)

References 60 publications

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“…Ferrets in all influenza virus groups developed fulminant clinical signs of IAV infection (Supplementary Fig. S8) and reached peak shed viral loads of 10 5 -10 6 TCID 50 units/ml nasal lavage 2 dpi (Extended Data Fig. 6a).…”

Section: Main Textmentioning

confidence: 99%

“…MeV-induced immune amnesia is not mitigated by post-exposure vaccination and the impact of unrelated respiratory virus disease history on measles severity has not been defined. We used a lethal canine distemper virus (CDV)-ferret model as surrogate for human morbillivirus disease 5 and employed the orally efficacious broad-spectrum paramyxovirus polymerase inhibitor GHP-88309 6 to establish measles treatment paradigms. Applying a receptor tropism-intact recombinant CDV with low lethality, we provide in vivo confirmation of the morbillivirus immune amnesia hypothesis and reveal an 8-day advantage of antiviral treatment versus therapeutic vaccination in preserving immune memory.…”

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confidence: 99%

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Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Cox,

Wolf,

Lieberman

et al. 2023

Preprint

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SummaryAfter years of the COVID-19 pandemic, over 40 million children worldwide are at risk of measles due to delayed vaccination1and temporary SARS-CoV-2 viral dominance2. Acute measles has a case-fatality rate of ∼1%, but most morbidity and mortality arise post-measles due to destruction of pre-existing immune memory by lymphotropic measles virus (MeV)3,4, a paramyxovirus of theMorbillivirusgenus. MeV-induced immune amnesia is not mitigated by post-exposure vaccination and the impact of unrelated respiratory virus disease history on measles severity has not been defined. We used a lethal canine distemper virus (CDV)-ferret model as surrogate for human morbillivirus disease5and employed the orally efficacious broad-spectrum paramyxovirus polymerase inhibitor GHP-883096to establish measles treatment paradigms. Applying a receptor tropism-intact recombinant CDV with low lethality, we providein vivoconfirmation of the morbillivirus immune amnesia hypothesis and reveal an 8-day advantage of antiviral treatment versus therapeutic vaccination in preserving immune memory. Infection of ferrets with non-lethal influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks prior to CDV caused exacerbated CDV disease that rapidly advanced to fatal hemorrhagic pneumonia associated with lung onslaught by commensal bacteria. RNAseq of BAL samples and lung tissue identified CDV-induced expression of trefoil factor (TFF) peptides, which was absent in animals pre-infected with IAV, thus highlighting that immune priming by unrelated respiratory viruses influences morbillivirus infection outcome. Non-invasive pulmonary ferret MRI revealed that severe outcomes of consecutive IAV/CDV infections were prevented by oral GHP-88309 treatment even when initiated after peak clinical signs of CDV. These findings validate the morbillivirus immune amnesia hypothesis, define treatment paradigms for measles, identify prior disease history as risk factor for exacerbated morbillivirus disease, and demonstrate that treating morbillivirus infection with direct-acting oral antivirals provides therapeutic benefit regardless of whether the time window to mitigate primary clinical signs of infection has closed.

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Section: Main Textmentioning

confidence: 99%

mentioning

confidence: 99%

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Cox,

Wolf,

Lieberman

et al. 2023

Preprint

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“…Those affected are puppies between three and six months of age, since their immune system is poorly developed and they have already lost the main maternal results [4,6]. The virus enters the respiratory tract and during the first 24 hours it affects the regional lymph nodes and after 7 days all the lymphoid tissue, producing immunosuppression due to the decrease in the appearance of T and B lymphocytes [3]. In the following weeks, the animal may recover or present symptoms associated with a secondary viremia, since the infected mononuclear cells transport the virus to the epithelial surface of the digestive, respiratory, urogenital, and cutaneous and/or central nervous system tracts, with the respective clinical manifestations of each affected organ [5].…”

Section: Pathogenymentioning

confidence: 99%

“…The F and H proteins are integral proteins of the lipid envelope membrane, associated with the M protein, which carry out the interaction between the RNP complex and the membrane. In addition to this, integral membrane proteins are responsible for virion recognition for entry into host cells, being the main targets of the immune system [2,3]. In vitro studies have also shown that hemagglutinin, the protein, is the main determinant of cell tropism [4].…”

Section: Introductionmentioning

confidence: 99%

Primers design for the detection and genotyping of the Canine Distemper Virus

Garrido¹,

Ma²,

Navarro³

2022

World J. Bio. Pharm. Health Sci.

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Canine Distemper Virus (CDV) has potential hosts, all carnivores, including wild animals. The associated disease, called canine distemper (CD) has a high prevalence and is highly contagious, being one of the main causes of death in domestic and wild canids. Although it is a monotypic virus, that is, with little genetic preference, the H gene has a high genetic variation, which would produce different strains of the virus, some more virulent than others and with different tropism. It is because of this specific specification that patients still get sick, despite being vaccinated, since the eightfold vaccine protects against one strain of the virus: America-1. Thus, any carnivore susceptible to the virus that is confronted with a strain against which it has not been vaccinated is as likely to become ill as an animal that has simply never been vaccinated against this viral disease. To face this situation, it is essential to know the characteristics of the genotypes of the virus present in the country. Through previous studies, it is known that in Chile there are at least two of the fourteen VDC lineages, but this does not imply that they are the only ones in the country, which is why it is proposed to propose a prior Polymerase Chain Reaction protocol. Reverse transcription using both matches for the N gene and for the H gene (lineages: America-1 and European) to shed light on the genotype found in the samples, which may not even belong to either of the two lineages described above in the country. For the generation of an RT-PCR protocol capable of detecting VDC, the use of the Genbank® genomic database in conjunction with the in silico design of primers is very interesting, indicating whether it corresponds to the American-1 or European lineage.

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Ferret Pediatrics

Wyre

2024

Veterinary Clinics of North America: Exotic Animal Practice

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The Ferret in Morbillivirus Research

Cited by 4 publications

References 60 publications

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets

Primers design for the detection and genotyping of the Canine Distemper Virus

Ferret Pediatrics

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