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 Koka, P. S.
Right arrow Articles by Zack, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Koka, P. S.
Right arrow Articles by Zack, J. A.

 Previous Article  |  Next Article 

J Virol, June 1998, p. 5121-5127, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Human Immunodeficiency Virus Inhibits Multilineage Hematopoiesis In Vivo

Prasad S. Koka,1 John K. Fraser,1 Yvonne Bryson,2 Gregory C. Bristol,1 Grace M. Aldrovandi,1,dagger Eric S. Daar,3 and Jerome A. Zack1,*

Division of Hematology-Oncology, Department of Medicine, UCLA School of Medicine and Jonsson Comprehensive Cancer Center,1 and Department of Pediatrics, UCLA School of Medicine,2 Los Angeles, California 90095, and Division of Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, California 900483

Received 6 January 1998/Accepted 3 March 1998

Human immunodeficiency virus type 1 (HIV-1)-infected individuals often exhibit multiple hematopoietic abnormalities reaching far beyond loss of CD4+ lymphocytes. We used the SCID-hu (Thy/Liv) mouse (severe combined immunodeficient mouse transplanted with human fetal thymus and liver tissues), which provides an in vivo system whereby human pluripotent hematopoietic progenitor cells can be maintained and undergo T-lymphoid differentiation and wherein HIV-1 infection causes severe depletion of CD4-bearing human thymocytes. Herein we show that HIV-1 infection rapidly and severely decreases the ex vivo recovery of human progenitor cells capable of differentiation into both erythroid and myeloid lineages. However, the total CD34+ cell population is not depleted. Combination antiretroviral therapy administered well after loss of multilineage progenitor activity reverses this inhibitory effect, establishing a causal role of viral replication. Taken together, our results suggest that pluripotent stem cells are not killed by HIV-1; rather, a later stage important in both myeloid and erythroid differentiation is affected. In addition, a primary virus isolated from a patient exhibiting multiple hematopoietic abnormalities preferentially depleted myeloid and erythroid colony-forming activity rather than CD4-bearing thymocytes in this system. Thus, HIV-1 infection perturbs multiple hematopoietic lineages in vivo, which may explain the many hematopoietic defects found in infected patients.

* Corresponding author. Mailing address: Division of Hematology-Oncology, Department of Medicine, 11-934 Factor Building, UCLA School of Medicine and Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095-1678. Phone: (310) 794-7765. Fax: (310) 825-6192. E-mail: jzack{at}ucla.edu.

dagger Present address: UAB AIDS Center, University of Alabama, Birmingham, AL 35294.

J Virol, June 1998, p. 5121-5127, Vol. 72, No. 6
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Redd, A. D., Avalos, A., Essex, M. (2007). Infection of hematopoietic progenitor cells by HIV-1 subtype C, and its association with anemia in southern Africa. Blood 110: 3143-3149 [Abstract] [Full Text]  
  • Watanabe, S., Terashima, K., Ohta, S., Horibata, S., Yajima, M., Shiozawa, Y., Dewan, M. Z., Yu, Z., Ito, M., Morio, T., Shimizu, N., Honda, M., Yamamoto, N. (2007). Hematopoietic stem cell-engrafted NOD/SCID/IL2R{gamma}null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses. Blood 109: 212-218 [Abstract] [Full Text]  
  • Wu, W., Vieira, J., Fiore, N., Banerjee, P., Sieburg, M., Rochford, R., Harrington, W. Jr, Feuer, G. (2006). KSHV/HHV-8 infection of human hematopoietic progenitor (CD34+) cells: persistence of infection during hematopoiesis in vitro and in vivo. Blood 108: 141-151 [Abstract] [Full Text]  
  • Williams, C. A., Mondal, D., Agrawal, K. C. (2005). The HIV-1 Tat Protein Enhances Megakaryocytic Commitment of K562 Cells by Facilitating CREB Transcription Factor Coactivation by CBP. Exp. Biol. Med. 230: 872-884 [Abstract] [Full Text]  
  • Tripp, A., Liu, Y., Sieburg, M., Montalbano, J., Wrzesinski, S., Feuer, G. (2003). Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34+ Cells In Vitro. J. Virol. 77: 12152-12164 [Abstract] [Full Text]  
  • Azzoni, L., Papasavvas, E., Chehimi, J., Kostman, J. R., Mounzer, K., Ondercin, J., Perussia, B., Montaner, L. J. (2002). Sustained Impairment of IFN-{gamma} Secretion in Suppressed HIV-Infected Patients Despite Mature NK Cell Recovery: Evidence for a Defective Reconstitution of Innate Immunity. J. Immunol. 168: 5764-5770 [Abstract] [Full Text]  
  • Scadden, D. T., Shen, H., Cheng, T. (2000). Hematopoietic Stem Cells in HIV Disease. J Natl Cancer Inst Monogr 2000: 24-29 [Abstract] [Full Text]  
  • Clark, D. R., Repping, S., Pakker, N. G., Prins, J. M., Notermans, D. W., Wit, F. W. N. M., Reiss, P., Danner, S. A., Coutinho, R. A., Lange, J. M. A., Miedema, F. (2000). T-cell progenitor function during progressive human immunodeficiency virus-1 infection and after antiretroviral therapy. Blood 96: 242-249 [Abstract] [Full Text]  
  • Koka, P. S., Jamieson, B. D., Brooks, D. G., Zack, J. A. (1999). Human Immunodeficiency Virus Type 1-Induced Hematopoietic Inhibition Is Independent of Productive Infection of Progenitor Cells In Vivo. J. Virol. 73: 9089-9097 [Abstract] [Full Text]  
  • Amado, R. G., Jamieson, B. D., Cortado, R., Cole, S. W., Zack, J. A. (1999). Reconstitution of Human Thymic Implants Is Limited by Human Immunodeficiency Virus Breakthrough during Antiretroviral Therapy. J. Virol. 73: 6361-6369 [Abstract] [Full Text]  
  • Kovalev, G., Duus, K., Wang, L., Lee, R., Bonyhadi, M., Ho, D., McCune, J. M., Kaneshima, H., Su, L. (1999). Induction of MHC Class I Expression on Immature Thymocytes in HIV-1-Infected SCID-hu Thy/Liv Mice: Evidence of Indirect Mechanisms. J. Immunol. 162: 7555-7562 [Abstract] [Full Text]  
  • Mattapallil, J. J., Smit-McBride, Z., Dandekar, S. (1999). Gastrointestinal Epithelium Is an Early Extrathymic Site for Increased Prevalence of CD34+ Progenitor Cells in Contrast to the Thymus during Primary Simian Immunodeficiency Virus Infection. J. Virol. 73: 4518-4523 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»