Human immunodeficiency virus infection of human placental cord blood CD34(+)AC133(+) stem cells and their progeny

The AC133 is a novel antigen selectively expressed on primitive CD34(bright ) Stem cells and is a valuable marker for the selection of long-term cultur e-initiating cells (LTC-ICs) and severe combined immunodeficiency (SCID)-re populating cells, Human placental cord blood (HPCB) is a rich source of CD3 4(+)AC133(+) cells. Since AC133 antibody is likely to be used as an alterna tive 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. Fre shly isolated HPCB CD34(+)AC133(+) stem cells were not susceptible to HIV-1 infection as determined by PCR and reverse transcriptase assays, Inoculati on with HIV-1 did not affect the viability and clonogenic ability of HPCB C D34(+)AC133(+) cells. Although the highly purified HPCB CD34(+)AC133(+) ste m cells contained mRNA for CD4 and CXCR4 receptors, CD4 and CXCR4 proteins were not expressed on these cells, Similarly, CCR5 protein, the major macro phage-tropic HIV-1 coreceptor, was not expressed in freshly isolated HPCB C D34(+)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 corr elated with susceptibility to HIV-1 infection in vitro, These findings sugg est that freshly isolated HPCB CD34(+)AC133(+) stem cells are not susceptib le to HIV-1 infection and may not be a viral reservoir, These data have imp ortant implications for the use of AC133 antibody as a means of enriching f or primitive hematopoietic stem cells from placental cord blood and in the design of stem cell or progenitor cell-based gene therapeutic strategies fo r perinatal HIV-1 infection.