This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Slobedman, B.
Right arrow Articles by Mocarski, E. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Slobedman, B.
Right arrow Articles by Mocarski, E. S.

 Previous Article  |  Next Article 

Journal of Virology, June 1999, p. 4806-4812, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Quantitative Analysis of Latent Human Cytomegalovirus

Barry Slobedman and Edward S. Mocarski*

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5124

Received 17 December 1998/Accepted 2 March 1999

Cytomegalovirus latency depends on an interaction with hematopoietic cells in bone marrow and peripheral blood. The distribution of viral DNA was investigated by PCR-driven in situ hybridization (PCR-ISH), and the number of viral genomes per cell was estimated by quantitative competitive PCR during both experimental and natural latent infection. During experimental latent infection of cultured granulocyte-macrophage progenitors, the viral genome was detected in >90% of cells at a copy number of 1 to 8 viral genomes per cell. During natural infection, viral genomes were detected in 0.004 to 0.01% of mononuclear cells from granulocyte colony-stimulating factor-mobilized peripheral blood or bone marrow from seropositive donors, at a copy number of 2 to 13 genomes per infected cell. When evaluated by reverse transcription-PCR-ISH, only a small proportion of experimentally infected cells (approximately 2%) had detectable latent transcripts. This investigation identifies the small percentage of bone marrow-derived mononuclear cells that become latently infected during natural infection and suggests that latency may proceed in some cells that fail to encode currently identified latent transcripts.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124. Phone: (650) 723-6435. Fax: (650) 723-1606. E-mail: mocarski{at}stanford.edu.


Journal of Virology, June 1999, p. 4806-4812, Vol. 73, No. 6
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Cheung, A. K. L., Gottlieb, D. J., Plachter, B., Pepperl-Klindworth, S., Avdic, S., Cunningham, A. L., Abendroth, A., Slobedman, B. (2009). The role of the human cytomegalovirus UL111A gene in down-regulating CD4+ T-cell recognition of latently infected cells: implications for virus elimination during latency. Blood 114: 4128-4137 [Abstract] [Full Text]  
  • Seckert, C. K., Renzaho, A., Tervo, H.-M., Krause, C., Deegen, P., Kuhnapfel, B., Reddehase, M. J., Grzimek, N. K. A. (2009). Liver Sinusoidal Endothelial Cells Are a Site of Murine Cytomegalovirus Latency and Reactivation. J. Virol. 83: 8869-8884 [Abstract] [Full Text]  
  • Petrucelli, A., Rak, M., Grainger, L., Goodrum, F. (2009). Characterization of a Novel Golgi Apparatus-Localized Latency Determinant Encoded by Human Cytomegalovirus. J. Virol. 83: 5615-5629 [Abstract] [Full Text]  
  • Crough, T., Khanna, R. (2009). Immunobiology of Human Cytomegalovirus: from Bench to Bedside. Clin. Microbiol. Rev. 22: 76-98 [Abstract] [Full Text]  
  • Stern, J. L., Slobedman, B. (2008). Human Cytomegalovirus Latent Infection of Myeloid Cells Directs Monocyte Migration by Up-Regulating Monocyte Chemotactic Protein-1. J. Immunol. 180: 6577-6585 [Abstract] [Full Text]  
  • Mitchell, D. A., Xie, W., Schmittling, R., Learn, C., Friedman, A., McLendon, R. E., Sampson, J. H. (2008). Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma. Neuro Oncol Duke 10: 10-18 [Abstract] [Full Text]  
  • Potena, L., Holweg, C. T. J., Vana, M. L., Bashyam, L., Rajamani, J., McCormick, A. L., Cooke, J. P., Valantine, H. A., Mocarski, E. S. (2007). Frequent Occult Infection with Cytomegalovirus in Cardiac Transplant Recipients despite Antiviral Prophylaxis. J. Clin. Microbiol. 45: 1804-1810 [Abstract] [Full Text]  
  • Cheung, A. K. L., Abendroth, A., Cunningham, A. L., Slobedman, B. (2006). Viral gene expression during the establishment of human cytomegalovirus latent infection in myeloid progenitor cells. Blood 108: 3691-3699 [Abstract] [Full Text]  
  • Frascaroli, G., Varani, S., Moepps, B., Sinzger, C., Landini, M. P., Mertens, T. (2006). Human cytomegalovirus subverts the functions of monocytes, impairing chemokine-mediated migration and leukocyte recruitment.. J. Virol. 80: 7578-7589 [Abstract] [Full Text]  
  • Sinclair, J., Sissons, P. (2006). Latency and reactivation of human cytomegalovirus. J. Gen. Virol. 87: 1763-1779 [Abstract] [Full Text]  
  • Reeves, M. B., Lehner, P. J., Sissons, J. G. P., Sinclair, J. H. (2005). An in vitro model for the regulation of human cytomegalovirus latency and reactivation in dendritic cells by chromatin remodelling. J. Gen. Virol. 86: 2949-2954 [Abstract] [Full Text]  
  • Reeves, M. B., MacAry, P. A., Lehner, P. J., Sissons, J. G. P., Sinclair, J. H. (2005). Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc. Natl. Acad. Sci. USA 102: 4140-4145 [Abstract] [Full Text]  
  • Simon, C. O., Seckert, C. K., Dreis, D., Reddehase, M. J., Grzimek, N. K. A. (2005). Role for Tumor Necrosis Factor Alpha in Murine Cytomegalovirus Transcriptional Reactivation in Latently Infected Lungs. J. Virol. 79: 326-340 [Abstract] [Full Text]  
  • Gredmark, S., Tilburgs, T., Soderberg-Naucler, C. (2004). Human Cytomegalovirus Inhibits Cytokine-Induced Macrophage Differentiation. J. Virol. 78: 10378-10389 [Abstract] [Full Text]  
  • Slobedman, B., Stern, J. L., Cunningham, A. L., Abendroth, A., Abate, D. A., Mocarski, E. S. (2004). Impact of Human Cytomegalovirus Latent Infection on Myeloid Progenitor Cell Gene Expression. J. Virol. 78: 4054-4062 [Abstract] [Full Text]  
  • Jenkins, C., Abendroth, A., Slobedman, B. (2004). A Novel Viral Transcript with Homology to Human Interleukin-10 Is Expressed during Latent Human Cytomegalovirus Infection. J. Virol. 78: 1440-1447 [Abstract] [Full Text]  
  • Visconti, M. R., Pennington, J., Garner, S. F., Allain, J.-P., Williamson, L. M. (2004). Assessment of removal of human cytomegalovirus from blood components by leukocyte depletion filters using real-time quantitative PCR. Blood 103: 1137-1139 [Abstract] [Full Text]  
  • Hertel, L., Lacaille, V. G., Strobl, H., Mellins, E. D., Mocarski, E. S. (2003). Susceptibility of Immature and Mature Langerhans Cell-Type Dendritic Cells to Infection and Immunomodulation by Human Cytomegalovirus. J. Virol. 77: 7563-7574 [Abstract] [Full Text]  
  • Kondo, K., Sashihara, J., Shimada, K., Takemoto, M., Amo, K., Miyagawa, H., Yamanishi, K. (2003). Recognition of a Novel Stage of Betaherpesvirus Latency in Human Herpesvirus 6. J. Virol. 77: 2258-2264 [Abstract] [Full Text]  
  • Slobedman, B., Mocarski, E. S., Arvin, A. M., Mellins, E. D., Abendroth, A. (2002). Latent cytomegalovirus down-regulates major histocompatibility complex class II expression on myeloid progenitors. Blood 100: 2867-2873 [Abstract] [Full Text]  
  • Kercher, L., Mitchell, B. M. (2002). Persisting Murine Cytomegalovirus Can Reactivate and Has Unique Transcriptional Activity in Ocular Tissue. J. Virol. 76: 9165-9175 [Abstract] [Full Text]  
  • Kondo, K., Shimada, K., Sashihara, J., Tanaka-Taya, K., Yamanishi, K. (2002). Identification of Human Herpesvirus 6 Latency-Associated Transcripts. J. Virol. 76: 4145-4151 [Abstract] [Full Text]  
  • Beisser, P. S., Laurent, L., Virelizier, J.-L., Michelson, S. (2001). Human Cytomegalovirus Chemokine Receptor Gene US28 Is Transcribed in Latently Infected THP-1 Monocytes. J. Virol. 75: 5949-5957 [Abstract] [Full Text]  
  • Hummel, M., Zhang, Z., Yan, S., DePlaen, I., Golia, P., Varghese, T., Thomas, G., Abecassis, M. I. (2001). Allogeneic Transplantation Induces Expression of Cytomegalovirus Immediate-Early Genes In Vivo: a Model for Reactivation from Latency. J. Virol. 75: 4814-4822 [Abstract] [Full Text]  
  • Grzimek, N. K. A., Dreis, D., Schmalz, S., Reddehase, M. J. (2001). Random, Asynchronous, and Asymmetric Transcriptional Activity of Enhancer-Flanking Major Immediate-Early Genes ie1/3 and ie2 during Murine Cytomegalovirus Latency in the Lungs. J. Virol. 75: 2692-2705 [Abstract] [Full Text]  
  • Wolf, D. G., Courcelle, C. T., Prichard, M. N., Mocarski, E. S. (2001). Distinct and separate roles for herpesvirus-conserved UL97 kinase in cytomegalovirus DNA synthesis and encapsidation. Proc. Natl. Acad. Sci. USA 98: 1895-1900 [Abstract] [Full Text]  
  • White, K. L., Slobedman, B., Mocarski, E. S. (2000). Human Cytomegalovirus Latency-Associated Protein pORF94 Is Dispensable for Productive and Latent Infection. J. Virol. 74: 9333-9337 [Abstract] [Full Text]  
  • Hengel, H., Reusch, U., Geginat, G., Holtappels, R., Ruppert, T., Hellebrand, E., Koszinowski, U. H. (2000). Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus. J. Virol. 74: 7861-7868 [Abstract] [Full Text]  
  • Clementi, M. (2000). Quantitative Molecular Analysis of Virus Expression and Replication. J. Clin. Microbiol. 38: 2030-2036 [Full Text]  
  • van den Pol, A. N., Mocarski, E., Saederup, N., Vieira, J., Meier, T. J. (1999). Cytomegalovirus Cell Tropism, Replication, and Gene Transfer in Brain. J. Neurosci. 19: 10948-10965 [Abstract] [Full Text]  
  • Kurz, S. K., Reddehase, M. J. (1999). Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency to Recurrence. J. Virol. 73: 8612-8622 [Abstract] [Full Text]