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Journal of Virology, February 2009, p. 1173-1183, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02102-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Repair of the UL21 Locus in Pseudorabies Virus Bartha Enhances the Kinetics of Retrograde, Transneuronal Infection In Vitro and In Vivo{triangledown} ,{dagger}

D. Curanovic,1 M. G. Lyman,1 C. Bou-Abboud,2 J. P. Card,2 and L. W. Enquist1*

Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544,1 Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 152172

Received 6 October 2008/ Accepted 13 November 2008

The attenuated pseudorabies virus (PRV) strain Bartha contains several characterized mutations that affect its virulence and ability to spread through neural circuits. This strain contains a small genomic deletion that abrogates anterograde spread and is widely used as a retrograde-restricted neural circuit tracer. Previous studies showed that the retrograde-directed spread of PRV Bartha is slower than that of wild-type PRV. We used compartmented neuronal cultures to characterize the retrograde defect and identify the genetic basis of the phenotype. PRV Bartha is not impaired in retrograde axonal transport, but transneuronal spread among neurons is diminished. Repair of the UL21 locus with wild-type sequence restored efficient transneuronal spread both in vitro and in vivo. It is likely that mutations in the Bartha UL21 gene confer defects that affect infectious particle production, causing a delay in spread to presynaptic neurons and amplification of infection. These events manifest as slower kinetics of retrograde viral spread in a neural circuit.


* Corresponding author. Mailing address: Department of Molecular Biology, Princeton University, 314 Schultz Laboratory, Princeton, NJ 08544. Phone: (609) 258-2415. Fax: (609) 258-1035. E-mail: lenquist{at}princeton.edu

{triangledown} Published ahead of print on 19 November 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.


Journal of Virology, February 2009, p. 1173-1183, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02102-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Curanovic, D., Enquist, L. W. (2009). Virion-Incorporated Glycoprotein B Mediates Transneuronal Spread of Pseudorabies Virus. J. Virol. 83: 7796-7804 [Abstract] [Full Text]