Abstract
Meleagrid herpesvirus 1 (MeHV-1 or turkey herpesvirus) has been widely used as a vaccine in commercial poultry. Initially, these vaccine applications were for the prevention of Marek’s disease resulting from Gallid herpesvirus 2 infections, while more recently MeHV-1 has been used as recombinant vector for other poultry infections. The construction of herpesvirus infectious clones that permit propagation and manipulation of the viral genome in bacterial hosts has advanced the studies of herpesviral genetics. The current study reports the construction of five MeHV-1 infectious clones. The in vitro properties of viruses recovered from these clones were indistinguishable from the parental MeHV-1. In contrast, the rescued MeHV-1 viruses were significantly attenuated when used in vivo. Complete sequencing of the infectious clones identified the absence of two regions of the MeHV-1 genome compared to the MeHV-1 reference sequence. These analyses determined the rescued viruses have seven genes, UL43, UL44, UL45, UL56, HVT071, sorf3 and US2 either partially or completely deleted. In addition, single nucleotide polymorphisms were identified in all clones compared with the MeHV-1 reference sequence. As a consequence of one of the polymorphisms identified in the UL13 gene, four of the rescued viruses were predicted to encode a serine/threonine protein kinase lacking two of three domains required for activity. Thus four of the recovered viruses have a total of eight missing or defective genes. The implications of these findings in the context of herpesvirus biology and infectious clone construction are discussed.
Similar content being viewed by others
References
M. Bublot, J. Sharma, in Marek’s Disease: An Evolving Problem, ed. by F. Davison, V. Nair (Academic Press, Oxford, 2004), pp. 168–185
R. Darteil, M. Bublot, E. Laplace, J.F. Bouquet, J.C. Audonnet, M. Riviere, Virology 211, 481–490 (1995)
S.K. Reddy, J.M. Sharma, J. Ahmad, D.N. Reddy, J.K. McMillen, S.M. Cook, M.A. Wild, R.D. Schwartz, Vaccine 14, 469–477 (1996)
V. Palya, I. Kiss, T. Tatar-Kis, T. Mato, B. Felfoldi, Y. Gardin, Avian Dis. 56, 282–287 (2012)
D. Lan, X. Shi, Y. Wang, C. Liu, M. Wang, H. Cui, G. Tian, J. Li, G. Tong, Wei Sheng Wu Xue Bao Acta microbiol. Sin. 49, 78–84 (2009)
L.S. Lambeth, Y. Zhao, L.P. Smith, L. Kgosana, V. Nair, Vaccine 27, 298–306 (2009)
W. Brune, M. Messerle, U.H. Koszinowski, Trends Genet. 16, 254–259 (2000)
H. Adler, M. Messerle, U.H. Koszinowski, Rev. Med. Virol. 13, 111–121 (2003)
R.N. Hall, J. Meers, E. Fowler, T. Mahony, Viruses 4, 211–235 (2012)
B.K. Tischer, B.B. Kaufer, J. Biomed. Biotechnol. 2012, 472537 (2012)
D. Schumacher, B.K. Tischer, W. Fuchs, N. Osterrieder, J. Virol. 74, 11088–11098 (2000)
S.J. Baigent, L.J. Petherbridge, L.P. Smith, Y. Zhao, P.M. Chesters, V.K. Nair, J. Gen. Virol. 87, 769–776 (2006)
L. Petherbridge, H. Xu, Y. Zhao, L.P. Smith, J. Simpson, S. Baigent, V. Nair, J. Virol. Methods 158, 11–17 (2009)
C.L. Afonso, E.R. Tulman, Z. Lu, L. Zsak, D.L. Rock, G.F. Kutish, J. Virol. 75, 971–978 (2001)
L. Petherbridge, A.C. Brown, S.J. Baigent, K. Howes, M.A. Sacco, N. Osterrieder, V.K. Nair, J. Virol. Methods 78, 13376–13380 (2004)
S.J. Spatz, Y. Zhao, L. Petherbridge, L.P. Smith, S.J. Baigent, V. Nair, Virus Genes 35, 753–766 (2007)
K.W. Jarosinski, N.G. Margulis, J.P. Kamil, S.J. Spatz, V.K. Nair, N. Osterrieder, J. Virol. 81, 10575–10587 (2007)
K.W. Jarosinski, N. Osterrieder, J. Virol. 84, 7911–7916 (2010)
S.J. Spatz, L.P. Smith, S. Baigent, L. Petherbridge, V. Nair, J. Gen. Virol. 92, 1500–1507 (2011)
K.A. Schat, H.G. Purchase, in A Laboratory Manual for the Isolation and Identification of Avian Pathogens, ed. by D.E. Swayne, J.R. Gilsson, M.W. Jackwood, J.E. Pearson, W.M. Reed (The American Association of Avain Pathologists, Kennett Square, 1998), pp. 223–234
A. Islam, B. Harrison, B.F. Cheetham, T.J. Mahony, P.L. Young, S.W. Walkden-Brown, J. Virol. Methods 119, 103–113 (2004)
K.J. Livak, T.D. Schmittgen, Methods 25, 402–408 (2001)
R.N. Hall, J. Meers, N. Mitter, E.V. Fowler, T.J. Mahony, Avian Dis. 57, 380–386 (2013)
M.J. Betts, R.B. Russell, M.R. Barnes, I.C. Gray, in Bioinformatics for Geneticists, ed. by M.R. Barnes, I.C. Grey (Wiley, Chichester, 2003), pp. 289–316
B.K. Tischer, D. Schumacher, D. Chabanne-Vautherot, V. Zelník, J.F. Vautherot, N. Osterrieder, J. Virol. 79, 5889–5899 (2005)
M. Bublot, E. Laplace, J.C. Audonnet, Acta Virol. 43, 181–185 (1999)
Y. Zhao, L. Petherbridge, L.P. Smith, S. Baigent, V. Nair, Virol. J. 5, 19 (2008)
G.L. Cano-Monreal, K.M. Wylie, F. Cao, J.E. Tavis, L.A. Morrison, Virology 392, 137–147 (2009)
C. Blondeau, N. Chbab, C. Beaumont, K. Courvoisier, N. Osterrieder, J.F. Vautherot, C. Denesvre, Vet. Res. 38, 419–433 (2007)
S.J. Spatz, Virus Res. 149, 135–142 (2010)
S.J. Spatz, J.D. Volkening, I.M. Gimeno, M. Heidari, R.L. Witter, Virus Genes 45, 526–536 (2012)
N. Jaramillo, E. Domingo, M.C. Munoz-Egea, E. Tabares, I. Gadea, The J. Gen. Virol. 94, 366–375 (2013)
S. Duffy, L.A. Shackelton, E.C. Holmes, Nat. Rev. Genet. 9, 267–276 (2008)
T. Van Loy, K. Thys, L. Tritsmans, L.J. Stuyver, PLoS One 8, e70950 (2013)
E. Domingo, J. Sheldon, C. Perales, Microbiol. Mol. Biol. Rev. 76, 159–216 (2012)
A.S. Lauring, J. Frydman, R. Andino, Nat. Rev. Microbiol. 11, 327–336 (2013)
Acknowledgments
This research was conducted within the Poultry CRC, established and supported under the Australian Government’s Cooperative Research Centres Program. R.N.H. was a recipient of an Australian Postgraduate Research Award.
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by Zhen F. Fu.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Mahony, T.J., Hall, R.N., Walkden-Brown, S. et al. Genomic deletions and mutations resulting in the loss of eight genes reduce the in vivo replication capacity of Meleagrid herpesvirus 1 . Virus Genes 51, 85–95 (2015). https://doi.org/10.1007/s11262-015-1216-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11262-015-1216-7