Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo.
An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.
Davis
B R
BR
Geraldine Brush Cancer Research Institute, Medical Research Institute, San Francisco, California.
Schwartz
D H
DH
Marx
J C
JC
Johnson
C E
CE
Berry
J M
JM
Lyding
J
J
Merigan
T C
TC
Zander
A
A
D004279:DNA, Viral / Q000032:analysis*; D006678:HIV / Q000235:genetics*; D015658:HIV Infections / Q000175:diagnosis* / Q000235:genetics; D006679:HIV Seropositivity / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000382:microbiology*; D006801:Humans; D008264:Macrophages / Q000382:microbiology; D009000:Monocytes / Q000382:microbiology; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D013601:T-Lymphocytes / Q000382:microbiology
D004279:DNA, Viral