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 Blankson, J. N.
Right arrow Articles by Siliciano, R. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Blankson, J. N.
Right arrow Articles by Siliciano, R. F.

 Previous Article  |  Next Article 

Journal of Virology, March 2007, p. 2508-2518, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02165-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Isolation and Characterization of Replication-Competent Human Immunodeficiency Virus Type 1 from a Subset of Elite Suppressors{triangledown}

Joel N. Blankson,1* Justin R. Bailey,1 Seema Thayil,1 Hung-Chih Yang,1 Kara Lassen,1 Jun Lai,1,2 Shiv K. Gandhi,1 Janet D. Siliciano,1 Thomas M. Williams,3 and Robert F. Siliciano1,2

Department of Medicine, Johns Hopkins University School of Medicine,1 Howard Hughes Medical Institute, Baltimore, Maryland 21205,2 Department of Pathology, University of New Mexico School of Medicine, and Tricore Reference Laboratories, Albuquerque, New Mexico 871313

Received 3 October 2006/ Accepted 28 November 2006

Elite suppressors (ES) are untreated human immunodeficiency virus type 1 (HIV-1)-infected individuals who control viremia to levels below the limit of detection of current assays. The mechanisms involved in this control have not been fully elucidated. Several studies have demonstrated that some ES are infected with defective viruses, but it remains unclear whether others are infected with replication-competent HIV-1. To answer this question, we used a sensitive coculture assay in an attempt to isolate replication-competent virus from a cohort of 10 ES. We successfully cultured six replication-competent isolates from 4 of the 10 ES. The frequency of latently infected cells in these patients was more than a log lower than that seen in patients on highly active antiretroviral therapy with undetectable viral loads. Full-length sequencing of all six isolates revealed no large deletions in any of the genes. A few mutations and small insertions and deletions were found in some isolates, but phenotypic analysis of the affected genes suggested that their function remained intact. Furthermore, all six isolates replicated as well as standard laboratory strains in vitro. The results suggest that some ES are infected with HIV-1 isolates that are fully replication competent and that long-term immunologic control of replication-competent HIV-1 is possible.


* Corresponding author. Mailing address: Broadway Research Bldg., Rm. 880, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205. Phone: (410) 955-7757. Fax: (443) 287-6218. E-mail: jblanks{at}jhmi.edu.

{triangledown} Published ahead of print on 6 December 2006.


Journal of Virology, March 2007, p. 2508-2518, Vol. 81, No. 5
0022-538X/07/$08.00+0     doi:10.1128/JVI.02165-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Valentine, L. E., Loffredo, J. T., Bean, A. T., Leon, E. J., MacNair, C. E., Beal, D. R., Piaskowski, S. M., Klimentidis, Y. C., Lank, S. M., Wiseman, R. W., Weinfurter, J. T., May, G. E., Rakasz, E. G., Wilson, N. A., Friedrich, T. C., O'Connor, D. H., Allison, D. B., Watkins, D. I. (2009). Infection with "Escaped" Virus Variants Impairs Control of Simian Immunodeficiency Virus SIVmac239 Replication in Mamu-B*08-Positive Macaques. J. Virol. 83: 11514-11527 [Abstract] [Full Text]  
  • Migueles, S. A., Weeks, K. A., Nou, E., Berkley, A. M., Rood, J. E., Osborne, C. M., Hallahan, C. W., Cogliano-Shutta, N. A., Metcalf, J. A., McLaughlin, M., Kwan, R., Mican, J. M., Davey, R. T. Jr., Connors, M. (2009). Defective Human Immunodeficiency Virus-Specific CD8+ T-Cell Polyfunctionality, Proliferation, and Cytotoxicity Are Not Restored by Antiretroviral Therapy. J. Virol. 83: 11876-11889 [Abstract] [Full Text]  
  • Nou, E., Zhou, Y., Nou, D. D., Blankson, J. N. (2009). Effective Downregulation of HLA-A*2 and HLA-B*57 by Primary Human Immunodeficiency Virus Type 1 Isolates Cultured from Elite Suppressors. J. Virol. 83: 6941-6946 [Abstract] [Full Text]  
  • Saez-Cirion, A., Sinet, M., Shin, S. Y., Urrutia, A., Versmisse, P., Lacabaratz, C., Boufassa, F., Avettand-Fenoel, V., Rouzioux, C., Delfraissy, J.-F., Barre-Sinoussi, F., Lambotte, O., Venet, A., Pancino, G., for the ANRS EP36 HIV Controllers Study Group, (2009). Heterogeneity in HIV Suppression by CD8 T Cells from HIV Controllers: Association with Gag-Specific CD8 T Cell Responses. J. Immunol. 182: 7828-7837 [Abstract] [Full Text]  
  • O'Connell, K. A., Han, Y., Williams, T. M., Siliciano, R. F., Blankson, J. N. (2009). Role of Natural Killer Cells in a Cohort of Elite Suppressors: Low Frequency of the Protective KIR3DS1 Allele and Limited Inhibition of Human Immunodeficiency Virus Type 1 Replication In Vitro. J. Virol. 83: 5028-5034 [Abstract] [Full Text]  
  • Miura, T., Brumme, C. J., Brockman, M. A., Brumme, Z. L., Pereyra, F., Block, B. L., Trocha, A., John, M., Mallal, S., Harrigan, P. R., Walker, B. D. (2009). HLA-Associated Viral Mutations Are Common in Human Immunodeficiency Virus Type 1 Elite Controllers. J. Virol. 83: 3407-3412 [Abstract] [Full Text]  
  • Miura, T., Brockman, M. A., Schneidewind, A., Lobritz, M., Pereyra, F., Rathod, A., Block, B. L., Brumme, Z. L., Brumme, C. J., Baker, B., Rothchild, A. C., Li, B., Trocha, A., Cutrell, E., Frahm, N., Brander, C., Toth, I., Arts, E. J., Allen, T. M., Walker, B. D. (2009). HLA-B57/B*5801 Human Immunodeficiency Virus Type 1 Elite Controllers Select for Rare Gag Variants Associated with Reduced Viral Replication Capacity and Strong Cytotoxic T-Lymphotye Recognition. J. Virol. 83: 2743-2755 [Abstract] [Full Text]  
  • Bailey, J. R., Brennan, T. P., O'Connell, K. A., Siliciano, R. F., Blankson, J. N. (2009). Evidence of CD8+ T-Cell-Mediated Selective Pressure on Human Immunodeficiency Virus Type 1 nef in HLA-B*57+ Elite Suppressors. J. Virol. 83: 88-97 [Abstract] [Full Text]  
  • Hatano, H., Delwart, E. L., Norris, P. J., Lee, T.-H., Dunn-Williams, J., Hunt, P. W., Hoh, R., Stramer, S. L., Linnen, J. M., McCune, J. M., Martin, J. N., Busch, M. P., Deeks, S. G. (2009). Evidence for Persistent Low-Level Viremia in Individuals Who Control Human Immunodeficiency Virus in the Absence of Antiretroviral Therapy. J. Virol. 83: 329-335 [Abstract] [Full Text]  
  • Miura, T., Brockman, M. A., Brumme, Z. L., Brumme, C. J., Pereyra, F., Trocha, A., Block, B. L., Schneidewind, A., Allen, T. M., Heckerman, D., Walker, B. D. (2009). HLA-Associated Alterations in Replication Capacity of Chimeric NL4-3 Viruses Carrying gag-protease from Elite Controllers of Human Immunodeficiency Virus Type 1. J. Virol. 83: 140-149 [Abstract] [Full Text]  
  • Miura, T., Brockman, M. A., Brumme, C. J., Brumme, Z. L., Carlson, J. M., Pereyra, F., Trocha, A., Addo, M. M., Block, B. L., Rothchild, A. C., Baker, B. M., Flynn, T., Schneidewind, A., Li, B., Wang, Y. E., Heckerman, D., Allen, T. M., Walker, B. D. (2008). Genetic Characterization of Human Immunodeficiency Virus Type 1 in Elite Controllers: Lack of Gross Genetic Defects or Common Amino Acid Changes. J. Virol. 82: 8422-8430 [Abstract] [Full Text]  
  • Bailey, J. R., O'Connell, K., Yang, H.-C., Han, Y., Xu, J., Jilek, B., Williams, T. M., Ray, S. C., Siliciano, R. F., Blankson, J. N. (2008). Transmission of Human Immunodeficiency Virus Type 1 from a Patient Who Developed AIDS to an Elite Suppressor. J. Virol. 82: 7395-7410 [Abstract] [Full Text]  
  • Emu, B., Sinclair, E., Hatano, H., Ferre, A., Shacklett, B., Martin, J. N., McCune, J. M., Deeks, S. G. (2008). HLA Class I-Restricted T-Cell Responses May Contribute to the Control of Human Immunodeficiency Virus Infection, but Such Responses Are Not Always Necessary for Long-Term Virus Control. J. Virol. 82: 5398-5407 [Abstract] [Full Text]  
  • Gandhi, S. K., Siliciano, J. D., Bailey, J. R., Siliciano, R. F., Blankson, J. N. (2008). Role of APOBEC3G/F-Mediated Hypermutation in the Control of Human Immunodeficiency Virus Type 1 in Elite Suppressors. J. Virol. 82: 3125-3130 [Abstract] [Full Text]  
  • Potter, S. J., Lacabaratz, C., Lambotte, O., Perez-Patrigeon, S., Vingert, B., Sinet, M., Colle, J.-H., Urrutia, A., Scott-Algara, D., Boufassa, F., Delfraissy, J.-F., Theze, J., Venet, A., Chakrabarti, L. A. (2007). Preserved Central Memory and Activated Effector Memory CD4+ T-Cell Subsets in Human Immunodeficiency Virus Controllers: an ANRS EP36 Study. J. Virol. 81: 13904-13915 [Abstract] [Full Text]