|MA, YUANMEI - The Ohio State University|
|WEI, YONGWEI - The Ohio State University|
|SUN, JING - The Ohio State University|
|RAUF, ABDUL - The Ohio State University|
|ZHANG, YU - The Ohio State University|
|SAIF, MO - The Ohio State University|
|YU, LIAN - Zhejian University|
|LI, JIANRONG - The Ohio State University|
Submitted to: American Society for Virology Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/10/2014
Publication Date: 6/25/2014
Citation: Ma, Y., Wei, Y., Sun, J., Rauf, A., Zhang, Y., Yu, Q., Saif, M., Yu, L., Li, J. 2014. Rational design of avian metapneumovirus live attenuated vaccines by inhibiting viral messenger RNA cap methyltransferase [abstract]. In: Proceedings of the 33rd Annual Meeting of American Society for Virology, June 21-25, 2014, Fort Collins, Colorado. p. 147.
Technical Abstract: Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis, is a non-segmented negative-sense RNA virus belonging to the family of Paramyxoviridae, the subfamily Pneumovirinae, and the genus Metapneumovirus. aMPV is the causative agent of respiratory tract infection and rhinotracheitis in turkeys, and is associated with swollen head syndrome in chickens. Since its discovery in the 1970s, aMPV has been recognized as an economically important pathogen in the poultry industry worldwide. The conserved region VI (CR-VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at guanine N-7 (G-N-7) and ribose 2’-O positions. In this study, we generated a panel of recombinant aMPV (raMPV) Colorado strains carrying mutations in the S-adenosyl methionine (SAM) binding site in the CR-VI of L protein. These recombinant viruses were specifically defective in ribose 2’-O, but not G-N-7 methylation, and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of specific-pathogen-free (SPF) young turkeys. Importantly, turkeys vaccinated with these MTase-defective raMPVs triggered a high level of neutralizing antibody and were completely protected from challenge with homologous aMPV Colorado strain and heterologous aMPV Minnesota strain. Collectively, our results indicate that (i) aMPV lacking 2’-O methylation is highly attenuated in vitro and in vivo, and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for aMPV, and perhaps other paramyxoviruses.