Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46
| العنوان: | Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46 |
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| المؤلفون: | Eiji Oishi, Risa Kainuma, Morimasa Yamanaka, Go Sehata, Sho Oshima, Hiroaki Sato, Tatsuhiko Igarashi, Taichi Noro, Takuo Takahashi |
| المصدر: | Journal of General Virology. 98:2759-2770 |
| بيانات النشر: | Microbiology Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Parvovirus, Canine, Virulence Factors, viruses, DNA Mutational Analysis, Host tropism, Virulence, Vaccines, Attenuated, medicine.disease_cause, Virus, Cell Line, Parvoviridae Infections, 03 medical and health sciences, Dogs, Serial passage, Virology, medicine, Animals, Dog Diseases, Serial Passage, Mutation, Attenuated vaccine, biology, Parvovirus, Canine parvovirus, Viral Vaccines, biology.organism_classification, 030104 developmental biology, Amino Acid Substitution, Animals, Newborn, Capsid Proteins |
| الوصف: | Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation in vivo, and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates. |
| تدمد: | 1465-2099 0022-1317 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea6c0441570cf3e800ffc70d8ad7d3ec https://doi.org/10.1099/jgv.0.000936 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ea6c0441570cf3e800ffc70d8ad7d3ec |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14652099 00221317 |
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