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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.


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