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Reactivation phenotype in rabbits of a herpes simplex virus type 1 mutant containing an unrelated antiapoptosis gene in place of latency-associated transcript

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Abstract

Latency-associated transcript (LAT) significantly enhances the spontaneous reactivation phenotype of herpes simplex virus type 1 (HSV-1). The mechanism by which LAT accomplishes this has been elusive. To determine if LAT’s antiapoptosis activity is involved, the authors used a rabbit eye model to analyze the spontaneous reactivation phenotype of an HSV-1 mutant in which LAT was replaced by an unrelated antiapoptosis gene. This virus, dLAT-cpIAP, contains the open reading frame of the baculovirus inhibitor of apoptosis protein gene (cpIAP) in place of LAT, under control of the LAT promoter. The authors report here that in a rabbit ocular model of infection, dLAT-cpIAP had a spontaneous reactivation phenotype similar to wild-type virus and significantly higher than LAT(−) viruses. This was consistent with their previous findings using the mouse trigeminal ganglia explant—induced reactivation model. Whether LAT (and in the case of dLAT-cpIAP, cpIAP) enhances the spontaneous reactivation phenotype by functioning during establishment of latency, maintenance of latency, or reactivation from latency, or during two or more of these periods, remains to be determined. Regardless, the results presented in this study strongly support the hypothesis that LAT’s antiapoptosis activity is the dominant function that enhances HSV-1’s spontaneous reactivation phenotype.

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Authors and Affiliations

  1. The Eye Institute, Department of Ophthalmology, University of California Irvine, School of Medicine, 92697, Irvine, CA, USA

    Ling Jin, Guey-Chuen Perng, Dale Carpenter, Kevin R. Mott, Nelson Osorio, Julia Naito, David J. Brick & Steven L. Wechsler

  2. Department of Veterinary and Biomedical Sciences, University of Nebraska, Lincoln, Nebraska, USA

    Clinton Jones

Authors
  1. Ling Jin
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  2. Guey-Chuen Perng
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  3. Dale Carpenter
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  4. Kevin R. Mott
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  5. Nelson Osorio
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  6. Julia Naito
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  7. David J. Brick
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  8. Clinton Jones
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  9. Steven L. Wechsler
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Corresponding author

Correspondence to Steven L. Wechsler.

Additional information

This work was supported by Public Health Service grants EY13191, EY12823, and P20RR15635; USDA grants 2005-01554 and 2006-01627; The Discovery Eye Foundation; The Henry L. Guenther Foundation; and Research to Prevent Blindness.

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Jin, L., Perng, GC., Carpenter, D. et al. Reactivation phenotype in rabbits of a herpes simplex virus type 1 mutant containing an unrelated antiapoptosis gene in place of latency-associated transcript. Journal of NeuroVirology 13, 78–84 (2007). https://doi.org/10.1080/13550280601164333

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  • DOI: https://doi.org/10.1080/13550280601164333

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