The AC133 is a novel
antigen selectively expressed on primitive CD34bright stem cells and is a valuable marker for the selection of long-term culture-initiating cells (LTC-ICs) and
severe combined immunodeficiency (SCID)-repopulating cells. Human placental cord blood (
HPCB) is a rich source of CD34+AC133+ cells. Since AC133 antibody is likely to be used as an alternative to CD34 for the selection of stem cells in transplant and gene therapy situations, we examined the susceptibility of
HPCB-isolated CD34+AC133+ stem cells to
infection with free and cell-associated HIV-1 in vitro. Freshly isolated
HPCB CD34+AC133+ stem cells were not susceptible to HIV-1
infection as determined by PCR and
reverse transcriptase assays. Inoculation with HIV-1 did not affect the viability and clonogenic ability of
HPCB CD34+AC133+ cells. Although the highly purified
HPCB CD34+AC133+ stem cells contained
mRNA for CD4 and
CXCR4 receptors, CD4 and CXCR4
proteins were not expressed on these cells. Similarly, CCR5
protein, the major macrophage-tropic HIV-1 coreceptor, was not expressed in freshly isolated
HPCB CD34+AC133+ stem cells, although the transcript for CCR5 was identified in these cells. Expression of CD4, CXCR4, and
CCR5 receptor proteins on the progeny derived from
HPCB CD34+AC133+ stem cells was detected and correlated with susceptibility to HIV-1
infection in vitro. These findings suggest that freshly isolated
HPCB CD34+AC133+ stem cells are not susceptible to HIV-1
infection and may not be a viral reservoir. These data have important implications for the use of AC133 antibody as a means of enriching for primitive hematopoietic stem cells from placental cord blood and in the design of stem cell or progenitor cell-based gene therapeutic strategies for perinatal HIV-1
infection.