Mutations within ICP4 acquired during in vitro attenuation do not alter virulence of recombinant Marek's disease viruses in vivo
Autor: | Hans H. Cheng, John R. Dunn, Evin Hildebrandt, Masahiro Niikura |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Candidate gene
Marek's disease virus viruses Mutant lcsh:QR1-502 Virulence Biology Recombinant virus medicine.disease_cause Biochemistry Virus lcsh:Microbiology Serial passage Virology medicine BAC Genetics Mutation Marek's disease Attenuation biology.organism_classification ICP4 Vaccine Horizontal transmission |
Zdroj: | Virology Reports, Vol 5, Iss C, Pp 10-18 (2015) |
ISSN: | 2214-6695 |
Popis: | Marek's disease (MD) is a T-cell lymphoma of chickens caused by the oncogenic Marek's disease virus (MDV). MD is primarily controlled by live-attenuated vaccines generated by repeated in vitro serial passage. Previous efforts to characterize attenuated MDVs identified numerous mutations, particularly a convergence of high-frequency mutations around amino acids 60–63 within ICP4 (RS1), therefore, ICP4 was considered a candidate gene deserving further characterization. Recombinant MDVs were generated containing a single Q63H mutation or double Q63H + S1630P mutations. Despite the repetitive nature of mutations within ICP4, neither recombinant virus decreased virulence, although one mutant reduced in vivo replication and failed to transmit horizontally. Our results indicate that these mutations are insufficient to reduce disease incidence in infected birds, and suggest that variants in ICP4 do not directly alter virulence, but rather may enhance MDV replication rates in vitro, offering an explanation for the widespread occurrence of ICP4 mutations in a variety of attenuated herpesviruses. |
Databáze: | OpenAIRE |
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