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 in 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 (granulocytic/macrophagic and erythroid) progenitors, whereas it significantly decreased the number of pluripotent (granulocytic/erythroid/ monocytic/megakaryocytic) progenitors. Such inhibitory effect was completely abrogated by incubating HHV-7 inoculum with anti-HHV-7 neutralizing serum. In liquid cultures, HHV-7 hastened maturation along the myeloid but not the erythroid lineage, 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 reaction (RT-PCR) in cells maturating along both the myeloid and the erythroid lineages. To evaluate the relevance of these in vitro findings, the presence of HHV-7 was investigated in bone marrow (BM) unfractionated mononuclear cells (MCs) as well as in purified CD34(+) and CD34(-) cell subsets, obtained 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 infects BM cells in vivo and shows the ability to affect the survival/differentiation of CD34(+) hematopoietic progenitors in vitro by inhibiting more ancestral progenitors and perturbing the maturation of myeloid cells.
Mirandola
P
P
Institute of Normal Morphology, G. D'Annunzio University of Chieti, Chieti, Italy.
Secchiero
P
P
Pierpaoli
S
S
Visani
G
G
Zamai
L
L
Vitale
M
M
Capitani
S
S
Zauli
G
G
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002460:Cell Line; D004261:DNA Replication; D004279:DNA, Viral / Q000032:analysis; D004912:Erythrocytes / Q000166:cytology / Q000821:virology; D005312:Fetal Blood / Q000166:cytology; D006098:Granulocytes / Q000166:cytology / Q000821:virology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000821:virology*; D016199:Herpesvirus 7, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes; D014779:Virus Replication
D015703:Antigens, CD; D018952:Antigens, CD34; D004279:DNA, Viral; D012333:RNA, Messenger