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Updated: Jun 13, 2026
Influenza A Virus Studies in a Mouse Model of Infection
Published on: September 7, 2017
Rational attenuation of canine distemper virus (CDV) to develop a morbillivirus animal model that mimics measles in
Katharina S Schmitz1, Linda J Rennick2, Natasha L Tilston-Lunel2
1Department of Viroscience, Erasmus MC, Rotterdam, the Netherlands.
Abstract:
Morbilliviruses are members of the family Paramyxoviridae and are known for their ability to cause systemic disease in a variety of mammalian hosts. The prototypic morbillivirus, measles virus (MeV), infects humans and still causes morbidity and mortality in unvaccinated children and young adults. Experimental infection studies in non-human primates have contributed to the understanding of measles pathogenesis. However, ethical restrictions call for the development of new animal models. Canine distemper virus (CDV) infects a wide range of animals, including ferrets, and its pathogenesis shares many features with measles. However, wild-type CDV infection is almost always lethal, while MeV infection is usually self-limiting. Here, we made five recombinant CDVs, predicted to be attenuated, and compared their pathogenesis to the non-attenuated recombinant CDV in a ferret model. Three viruses were insufficiently attenuated based on clinical signs, fatality, and systemic infection, while one virus was too attenuated. The last candidate virus caused a self-limiting infection associated with transient viremia and viral dissemination to all lymphoid tissues, was shed transiently from the upper respiratory tract, and did not result in acute neurological signs. Additionally, an in-depth phenotyping of the infected white blood cells showed lower infection percentages in all lymphocyte subsets when compared to the non-attenuated CDV. In conclusion, infection models using this candidate virus mimic measles and can be used to study pathogenesis-related questions and to test interventions for morbilliviruses in a natural host species.IMPORTANCEMorbilliviruses are transmitted via the respiratory route but cause systemic disease. The viruses use two cellular receptors to infect myeloid, lymphoid, and epithelial cells. Measles virus (MeV) remains an important cause of morbidity and mortality in humans, requiring animal models to study pathogenesis or intervention strategies. Experimental MeV infections in non-human primates are restricted by ethical and practical constraints, and animal morbillivirus infections in natural host species have been considered as alternatives. Inoculation of ferrets with wild-type canine distemper virus (CDV) has been used for this purpose, but in most cases, the virus overwhelms the immune system and causes highly lethal disease. Introduction of an additional transcription unit and an additional attenuating point mutation in the polymerase yielded a candidate virus that caused self-limiting disease with transient viremia and virus shedding. This rationally attenuated CDV strain can be used for experimental morbillivirus infections in ferrets that reflect measles in humans.
Insights
Researchers developed an attenuated canine distemper virus (CDV) in ferrets, creating a new animal model for studying morbilliviruses like measles virus (MeV). This model mimics MeV infection, aiding in pathogenesis research and intervention testing.
Area of Science:
- Virology
- Immunology
- Animal Models
Background:
- Morbilliviruses, including measles virus (MeV), cause significant human and animal disease.
- Current MeV pathogenesis studies are limited by ethical restrictions on non-human primate models.
- Canine distemper virus (CDV) shares pathogenesis similarities with MeV but is typically lethal in animal models.
Purpose of the Study:
- To develop and characterize attenuated recombinant canine distemper viruses (CDVs) for use as a ferret model of morbillivirus infection.
- To compare the pathogenesis of attenuated CDV candidates with wild-type CDV in ferrets.
- To identify a CDV strain that mimics measles virus infection for research purposes.
Main Methods:
- Construction and characterization of five recombinant CDVs with predicted attenuation.
- Infection of ferrets with recombinant CDVs and a non-attenuated control.
- Assessment of clinical signs, fatality rates, viral dissemination, shedding, and white blood cell phenotyping.
Main Results:
- Three of five recombinant CDVs were not sufficiently attenuated, showing severe disease.
- One candidate virus was overly attenuated, limiting its utility.
- A single recombinant CDV candidate induced self-limiting infection with transient viremia, shedding, and lymphoid tissue dissemination without acute neurological signs.
Conclusions:
- A rationally attenuated CDV strain was successfully developed, causing self-limiting disease in ferrets.
- This CDV model effectively mimics key aspects of measles virus infection.
- The developed ferret model provides a valuable platform for studying morbillivirus pathogenesis and evaluating therapeutic interventions.
