Avian metapneumovirus M2:2 protein inhibits replication in Vero cells: modification facilitates live vaccine development.
Throughout the world, avian metapneumovirus (AMPV) infection of subtype A is principally controlled by two live vaccines both derived from UK field strain #8544. Improvements of those vaccines by use of reverse genetics technology was found to be hampered by the inability of #8544 to replicate in the commonly exploited Vero cell based reverse genetics system. A systematic reverse genetics based genome modification of a DNA copy of #8544, employing sequence data from a Vero grown, #8544 derived, live vaccine; was used to determine mutations required to facilitate virus recovery and replication in Vero cells. This identified a single coding substitution in the M2:2 reading frame as responsible. Furthermore, ablation of M2:2 was found to elicit the same outcome. M2:2 sequence analysis of seven AMPVs found Vero cell adaption to be associated with non similar amino acid changes in M2:2. The study shows that M2:2 modification of field virus #8544 will enable research leading to improved vaccines. This may have more general application to other AMPV field strains.
Department of Infection Biology, Faculty of Health and Life Sciences, University of Liverpool, Leahurst Campus, Neston, Cheshire CH64 7TE, United Kingdom.
Jayne
J
Clubbe
Clive J
CJ
Naylor
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002522:Chlorocebus aethiops; D005814:Genes, Viral; D029121:Metapneumovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology*; D008969:Molecular Sequence Data; D020539:Sequence Analysis, Protein; D014709:Vero Cells; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014765:Viral Vaccines; D014779:Virus Replication
D014764:Viral Proteins; D014765:Viral Vaccines