Infection of CD34(+) hematopoietic progenitor cells by human herpesvirus 7(HHV-7)

To investigate the tropism of the T-lymphotropic human herpesvirus 7 (HHV-7 ) for hematopoietic progenitors, cord blood CD34(+) cells were inoculated i n vitro with HHV-7 and then induced to differentiate along the granulocytic and erythroid lineages by the addition of appropriate cytokine cocktails. In semisolid assays, HHV-7 modestly affected the growth of committed (granu locytic/macrophagic and erythroid) progenitors, whereas it significantly de creased the number of pluripotent (granulocytic/erythroid/ monocytic/megaka ryocytic) progenitors. Such inhibitory effect was completely abrogated by i ncubating HHV-7 inoculum with anti-HHV-7 neutralizing serum. In liquid cult ures, HHV-7 hastened maturation along the myeloid but not the erythroid lin eage, as demonstrated by the up-regulation of CD33 early myeloid antigen at day 7 of culture, and of CD15 and CD14 antigens at day 15. Moreover, HHV-7 messenger RNA was detected by reverse transcriptase-polymerase chain react ion (RT-PCR) in cells maturating along both the myeloid and the erythroid l ineages. To evaluate the relevance of these in vitro findings, the presence of HHV-7 was investigated in bone marrow (BM) unfractionated mononuclear c ells (MCs) as well as in purified CD34(+) and CD34(-) cell subsets, obtaine d from 14 normal adult donors. HHV-7 DNA was detected by DNA-PCR In 4 of 7 BMMC samples, and it was found to be associated with both the CD34(-) (2 of 7) and the CD34(+) (1 of 7) fractions. These data indicate that HHV-7 infe cts BM cells in vivo and shows the ability to affect the survival/different iation of CD34(+) hematopoietic progenitors in vitro by inhibiting more anc estral progenitors and perturbing the maturation of myeloid cells. (Blood. 2000;96:126-131) (C) 2000 by The American Society of Hematology.