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Journal of Virology, March 2009, p. 2417-2428, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02392-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Latent Species C Adenoviruses in Human Tonsil Tissues{triangledown} ,{dagger}

C. T. Garnett ,1,{ddagger},§ G. Talekar,1,{ddagger} J. A. Mahr,1,¶ W. Huang,1 Y. Zhang,1,|| D. A. Ornelles,2 and L. R. Gooding1*

Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, Georgia 30322,1 Wake Forest University School of Medicine, Department of Microbiology and Immunology, Winston-Salem, North Carolina 271572

Received 18 November 2008/ Accepted 18 December 2008

Although species C human adenoviruses establish persistent infections, the molecular details of this lifestyle remain poorly understood. We previously reported that adenovirus DNA is found in human mucosal T lymphocytes in a noninfectious form (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). In this study, human tonsil and adenoid tissues were analyzed to determine the dynamics of infection, the rate of clearance of viral DNA, and the possibility of reactivation of virus from these tissues. The presence of viral DNA peaked at 4 years of age and declined thereafter. The average number of viral genomes declined with the age of the donor. The frequency of virus-bearing cells ranged from 3 x 10–7 to 3.4 x 10–4, while the amount of viral DNA per cell varied less, with an average of 280 copies per cell. All species C serotypes were represented in these tissues, although adenovirus type 6 was notably rare. Infectious virus was detected infrequently (13 of 94 of donors tested), even among donors with the highest levels of adenoviral DNA. Adenovirus transcripts were rarely detected in uncultured lymphocytes (2 of 12 donors) but appeared following stimulation and culture (11 of 13 donors). Viral DNA replication could be stimulated in most donor samples by lymphocyte stimulation in culture. New infectious virus was detected in 13 of 15 donors following in vitro stimulation. These data suggest that species C adenoviruses can establish latent infections in mucosal lymphocytes and that stimulation of these cells can cause viral reactivation resulting in RNA transcription, DNA replication, and infectious virus production.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, 3107 Rollins Research Center, Emory University School of Medicine, Atlanta, GA 30322. Phone: (404) 727-5948. Fax: (404) 727-0293. E-mail: gooding{at}microbio.emory.edu

{triangledown} Published ahead of print on 24 December 2008.

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

{ddagger} These authors contributed equally to this study.

§ Present address: Georgia State University, Biology Department, Atlanta, GA.

Present address: The Scripps Research Institute, San Diego, CA.

|| Present address: Respiratory Branch, Centers for Disease Control and Prevention, Atlanta, GA.

Journal of Virology, March 2009, p. 2417-2428, Vol. 83, No. 6
0022-538X/09/$08.00+0     doi:10.1128/JVI.02392-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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