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Journal of Virology, July 2006, p. 6387-6398, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00352-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of Pseudorabies Virus Us3 Protein Kinase during Neuronal Infection

L. M. Olsen,1 T. H. Ch'ng,1 J. P. Card,2 and L. W. Enquist1*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Departments of Neuroscience and Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 152602

Received 20 February 2006/ Accepted 11 April 2006

The pseudorabies virus (PRV) Us3 gene is conserved among the alphaherpesviruses and encodes a serine/threonine protein kinase that is not required for growth in standard cell lines. In this report, we used a compartmented culture system to investigate the role of PRV Us3 in viral replication in neurons, in spread from neurons to PK15 cells, and in axon-mediated spread of infection. We also examined the role of Us3 in neuroinvasion and virulence in rodents. Us3 null mutants produce about 10-fold less infectious virus from neurons than wild-type virus and have no discernible phenotypes for axonal targeting of viral components in cultured peripheral nervous system neurons. After eye infection in rodents, Us3 null mutants were slightly attenuated for virulence, with a delayed onset of symptoms compared to the wild type or a Us3 null revertant. While initially delayed, the symptoms increased in severity until they approximated those of the wild-type virus. Us3 null mutants were neuroinvasive, spreading in both efferent and afferent circuits innervating eye tissues.


* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail: lenquist{at}princeton.edu.


Journal of Virology, July 2006, p. 6387-6398, Vol. 80, No. 13
0022-538X/06/$08.00+0     doi:10.1128/JVI.00352-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.







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