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Journal of Virology, October 2007, p. 11069-11074, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00243-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Spontaneous Reactivation of Herpes Simplex Virus Type 1 in Latently Infected Murine Sensory Ganglia{triangledown}

Todd P. Margolis,1,2* Fred L. Elfman,1,{dagger} David Leib,3 Nazzy Pakpour,1,{ddagger} Kathleen Apakupakul,1 Yumi Imai,1 and Cindy Voytek1,§

F. I. Proctor Foundation,1 Department of Ophthalmology, University of California San Francisco, Medical Sciences Building S-310, 513 Parnassus Ave, San Francisco, California 94143-0412,2 Department of Ophthalmology and Visual Sciences, Washington University, 660 South Euclid Ave., Box 8096, St. Louis, Missouri 631103

Received 5 February 2007/ Accepted 26 July 2007

Careful studies of mouse trigeminal ganglia (TG) latently infected with herpes simplex virus type 1 (HSV-1) indicate the presence of productive cycle viral gene products and persistent immune response, suggesting ongoing spontaneous viral reactivation in these tissues. In the present study we set out to determine whether infectious virus is present in murine TG latently infected with HSV-1 (KOS). At 37 days after ocular inoculation we found a small amount of infectious virus in ca. 6% of latently infected murine TG. Furthermore, the amount of infectious virus that we detected (PFU per viral antigen-positive neuron) was similar to that detected in acutely infected ganglia. We conclude that spontaneous reactivation of infectious HSV-1 occurs in the mouse TG and is likely the principle cause of viral protein expression in these tissues. We next examined the role of latency-associated transcript (LAT) in spontaneous ganglionic reactivation by examining ganglia latently infected with KOS dlLAT1.8, a LAT deletion virus. Through the use of immunocytochemistry we found that KOS dlLAT1.8 had a rate of spontaneous ganglionic reactivation very similar to that of HSV-1 (KOS). Studying spontaneous ganglionic reactivation of HSV in the mouse TG allows a direct study of viral reactivation from latently infected neurons without the potential confounders and complicating downstream events that accompany the study of viral reactivation by explantation or peripheral viral shedding. Since most cases of human viral shedding and reactivation are not associated with a known trigger, spontaneous ganglionic reactivation of HSV-1 may be a better model of human disease than existing models.

* Corresponding author. Mailing address: Francis I. Proctor Foundation, UCSF, Medical Sciences Building S-310, 513 Parnassus Ave., San Francisco, CA 94143-0412. Phone: (415) 476-4419. Fax: (415) 476-0527. E-mail: todd.margolis{at}ucsf.edu

{triangledown} Published ahead of print on 8 August 2007.

{dagger} Present address: 1543 Howard Ave., #1, Burlingame, CA 94010.

{ddagger} Present address: University of Pennsylvania, Hill Pavilion, 380 S., University Ave., Philadelphia, PA 19104-4539.

§ Deceased.

Journal of Virology, October 2007, p. 11069-11074, Vol. 81, No. 20
0022-538X/07/$08.00+0     doi:10.1128/JVI.00243-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mott, K. R., Bresee, C. J., Allen, S. J., BenMohamed, L., Wechsler, S. L., Ghiasi, H. (2009). Level of Herpes Simplex Virus Type 1 Latency Correlates with Severity of Corneal Scarring and Exhaustion of CD8+ T Cells in Trigeminal Ganglia of Latently Infected Mice. J. Virol. 83: 2246-2254 [Abstract] [Full Text]  
  • McMahon, R., Walsh, D. (2008). Efficient Quiescent Infection of Normal Human Diploid Fibroblasts with Wild-Type Herpes Simplex Virus Type 1. J. Virol. 82: 10218-10230 [Abstract] [Full Text]  


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