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 Pierson, T. C.
Right arrow Articles by Siliciano, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pierson, T. C.
Right arrow Articles by Siliciano, R. F.

 Previous Article  |  Next Article 

Journal of Virology, April 2002, p. 4138-4144, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.4138-4144.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Intrinsic Stability of Episomal Circles Formed during Human Immunodeficiency Virus Type 1 Replication

Theodore C. Pierson,1 Tara L. Kieffer,1 Christian T. Ruff,1 Christopher Buck,1 Stephen J. Gange,2 and Robert F. Siliciano1*

Department of Medicine, Johns Hopkins University School of Medicine,1 Department of Epidemiology, Johns Hopkins University School of Public Health, Baltimore, Maryland 212052

Received 9 August 2001/ Accepted 11 January 2002

The development of surrogate markers capable of detecting residual ongoing human immunodeficiency virus type 1 (HIV-1) replication in patients receiving highly active antiretroviral therapy is an important step in understanding viral dynamics and in developing new treatment strategies. In this study, we evaluated the utility of circular forms of the viral genome for the detection of recent infection of cells by HIV-1. We measured the fate of both one-long terminal repeat (1-LTR) and 2-LTR circles following in vitro infection of logarithmically growing CD4+ T cells under conditions in which cell death was not a significant contributing factor. Circular forms of the viral genome were found to be highly stable and to decrease in concentration only as a function of dilution resulting from cell division. We conclude that these DNA circles are not intrinsically unstable in all cell types and suggest that the utility of 2-LTR circle assays in measuring recent HIV-1 infection of susceptible cells in vivo needs to be reevaluated.


* Corresponding author. Mailing address: Department of Medicine, 1049 Ross Building, Johns Hopkins University School of Medicine, 720 Rutland Ave., Baltimore, MD 21205. Phone: (410) 955-2958. Fax: (410) 955-0964. E-mail: rsilicia{at}welch.jhu.edu.


Journal of Virology, April 2002, p. 4138-4144, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.4138-4144.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Kantor, B., Ma, H., Webster-Cyriaque, J., Monahan, P. E., Kafri, T. (2009). Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection. Proc. Natl. Acad. Sci. USA 106: 18786-18791 [Abstract] [Full Text]  
  • Goffinet, C., Allespach, I., Oberbremer, L., Golden, P. L., Foster, S. A., Johns, B. A., Weatherhead, J. G., Novick, S. J., Chiswell, K. E., Garvey, E. P., Keppler, O. T. (2009). Pharmacovirological Impact of an Integrase Inhibitor on Human Immunodeficiency Virus Type 1 cDNA Species In Vivo. J. Virol. 83: 7706-7717 [Abstract] [Full Text]  
  • Arfi, V., Lienard, J., Nguyen, X.-N., Berger, G., Rigal, D., Darlix, J.-L., Cimarelli, A. (2009). Characterization of the Behavior of Functional Viral Genomes during the Early Steps of Human Immunodeficiency Virus Type 1 Infection. J. Virol. 83: 7524-7535 [Abstract] [Full Text]  
  • Joos, B., Fischer, M., Kuster, H., Pillai, S. K., Wong, J. K., Boni, J., Hirschel, B., Weber, R., Trkola, A., Gunthard, H. F., The Swiss HIV Cohort Study, (2008). HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc. Natl. Acad. Sci. USA 105: 16725-16730 [Abstract] [Full Text]  
  • Carr, J. M., Cheney, K. M., Coolen, C., Davis, A., Shaw, D., Ferguson, W., Chang, G., Higgins, G., Burrell, C., Li, P. (2007). Development of Methods for Coordinate Measurement of Total Cell-Associated and Integrated Human Immunodeficiency Virus Type 1 (HIV-1) DNA Forms in Routine Clinical Samples: Levels Are Not Associated with Clinical Parameters, but Low Levels of Integrated HIV-1 DNA May Be Prognostic for Continued Successful Therapy. J. Clin. Microbiol. 45: 1288-1297 [Abstract] [Full Text]  
  • Brown, A., Zhang, H., Lopez, P., Pardo, C. A., Gartner, S. (2006). In vitro modeling of the HIV-macrophage reservoir. J. Leukoc. Biol. 80: 1127-1135 [Abstract] [Full Text]  
  • Cara, A., Klotman, M. E. (2006). Retroviral E-DNA: persistence and gene expression in nondividing immune cells. J. Leukoc. Biol. 80: 1013-1017 [Abstract] [Full Text]  
  • David, A., Saez-Cirion, A., Versmisse, P., Malbec, O., Iannascoli, B., Herschke, F., Lucas, M., Barre-Sinoussi, F., Mouscadet, J.-F., Daeron, M., Pancino, G. (2006). The Engagement of Activating Fc{gamma}Rs Inhibits Primate Lentivirus Replication in Human Macrophages. J. Immunol. 177: 6291-6300 [Abstract] [Full Text]  
  • Miles, L. R., Agresta, B. E., Khan, M. B., Tang, S., Levin, J. G., Powell, M. D. (2005). Effect of Polypurine Tract (PPT) Mutations on Human Immunodeficiency Virus Type 1 Replication: a Virus with a Completely Randomized PPT Retains Low Infectivity. J. Virol. 79: 6859-6867 [Abstract] [Full Text]  
  • Sharkey, M., Triques, K., Kuritzkes, D. R., Stevenson, M. (2005). In Vivo Evidence for Instability of Episomal Human Immunodeficiency Virus Type 1 cDNA. J. Virol. 79: 5203-5210 [Abstract] [Full Text]  
  • Gillim-Ross, L., Cara, A., Klotman, M. E. (2005). Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase inhibitors. J. Gen. Virol. 86: 765-771 [Abstract] [Full Text]  
  • Brussel, A., Sonigo, P. (2004). Evidence for Gene Expression by Unintegrated Human Immunodeficiency Virus Type 1 DNA Species. J. Virol. 78: 11263-11271 [Abstract] [Full Text]  
  • Serhan, F., Penaud, M., Petit, C., Leste-Lasserre, T., Trajcevski, S., Klatzmann, D., Duisit, G., Sonigo, P., Moullier, P. (2004). Early Detection of a Two-Long-Terminal-Repeat Junction Molecule in the Cytoplasm of Recombinant Murine Leukemia Virus-Infected Cells. J. Virol. 78: 6190-6199 [Abstract] [Full Text]  
  • Rector, A., Tachezy, R., Van Ranst, M. (2004). A Sequence-Independent Strategy for Detection and Cloning of Circular DNA Virus Genomes by Using Multiply Primed Rolling-Circle Amplification. J. Virol. 78: 4993-4998 [Abstract] [Full Text]  
  • Saenz, D. T., Loewen, N., Peretz, M., Whitwam, T., Barraza, R., Howell, K. G., Holmes, J. M., Good, M., Poeschla, E. M. (2004). Unintegrated Lentivirus DNA Persistence and Accessibility to Expression in Nondividing Cells: Analysis with Class I Integrase Mutants. J. Virol. 78: 2906-2920 [Abstract] [Full Text]  
  • Lu, R., Nakajima, N., Hofmann, W., Benkirane, M., Teh-Jeang, K., Sodroski, J., Engelman, A. (2004). Simian Virus 40-Based Replication of Catalytically Inactive Human Immunodeficiency Virus Type 1 Integrase Mutants in Nonpermissive T Cells and Monocyte-Derived Macrophages. J. Virol. 78: 658-668 [Abstract] [Full Text]  
  • Wilkinson, R. C., Murrell, C. K., Guy, R., Davis, G., Hall, J. M., North, D. C., Rose, N. J., Almond, N. (2003). Persistence and Dissemination of Simian Retrovirus Type 2 DNA in Relation to Viremia, Seroresponse, and Experimental Transmissibility in Macaca fascicularis. J. Virol. 77: 10751-10759 [Abstract] [Full Text]  
  • Brussel, A., Sonigo, P. (2003). Analysis of Early Human Immunodeficiency Virus Type 1 DNA Synthesis by Use of a New Sensitive Assay for Quantifying Integrated Provirus. J. Virol. 77: 10119-10124 [Abstract] [Full Text]  
  • Delelis, O., Saib, A., Sonigo, P. (2003). Biphasic DNA Synthesis in Spumaviruses. J. Virol. 77: 8141-8146 [Abstract] [Full Text]  
  • Stebbing, J., Gazzard, B., Kim, L., Portsmouth, S., Wildfire, A., Teo, I., Nelson, M., Bower, M., Gotch, F., Shaunak, S., Srivastava, P., Patterson, S. (2003). The heat-shock protein receptor CD91 is up-regulated in monocytes of HIV-1-infected "true" long-term nonprogressors. Blood 101: 4000-4004 [Abstract] [Full Text]  
  • Van Maele, B., De Rijck, J., De Clercq, E., Debyser, Z. (2003). Impact of the Central Polypurine Tract on the Kinetics of Human Immunodeficiency Virus Type 1 Vector Transduction. J. Virol. 77: 4685-4694 [Abstract] [Full Text]  
  • Strain, M. C., Gunthard, H. F., Havlir, D. V., Ignacio, C. C., Smith, D. M., Leigh-Brown, A. J., Macaranas, T. R., Lam, R. Y., Daly, O. A., Fischer, M., Opravil, M., Levine, H., Bacheler, L., Spina, C. A., Richman, D. D., Wong, J. K. (2003). Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: Intrinsic stability predicts lifelong persistence. Proc. Natl. Acad. Sci. USA 100: 4819-4824 [Abstract] [Full Text]  
  • Poon, B., Chen, I. S. Y. (2003). Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA. J. Virol. 77: 3962-3972 [Abstract] [Full Text]  
  • Buckman, J. S., Bosche, W. J., Gorelick, R. J. (2002). Human Immunodeficiency Virus Type 1 Nucleocapsid Zn2+ Fingers Are Required for Efficient Reverse Transcription, Initial Integration Processes, and Protection of Newly Synthesized Viral DNA. J. Virol. 77: 1469-1480 [Abstract] [Full Text]  
  • Butler, S. L., Johnson, E. P., Bushman, F. D. (2002). Human Immunodeficiency Virus cDNA Metabolism: Notable Stability of Two-Long Terminal Repeat Circles. J. Virol. 76: 3739-3747 [Abstract] [Full Text]