Inhibition of cord blood cell expansion by human herpesvirus 6 in vitro.
To elucidate the role of human herpesvirus 6 (HHV-6) in hematopoiesis, the influence of HHV-6A and HHV-6B on the in vitro expansion and differentiation of cord blood (CB) progenitor cells was investigated in liquid culture. Nonfractionated CB mononuclear cells (CB-MNC) or MACS-enriched CD34+ CB cells were seeded in liquid culture under conditions allowing maximal expansion of nucleated cells. Cells were either incubated with HHV-6A- or HHV-6B-containing cell culture supernatants or a virus-free control. After 7, 14, and 21 days, cells were analyzed for growth by cell count, for differentiation by flow cytometry, and for HHV-6 infection by antigen detection or PCR. Expansion of CB-MNC was significantly inhibited by HHV-6A and HHV-6B for a period of 3 weeks, including reduced proportions of CD34+ and CD33+ cells in HHV-6-treated cultures on day 7. In contrast, when starting with enriched CD34+ cells, the expansion was only affected by HHV-6A. Inhibition of CD34 and CD33 cell development was less pronounced in these cultures compared to CB-MNC cultures. However, HHV-6 antigen and DNA was detectable in these cultures. In conclusion, although HHV-6A inhibited expansion of CD34 progenitor cells, HHV-6B inhibited growth of immature CB cells only in interaction with nonfractionated CB-MNC.
Nitsche
Andreas
A
Medizinische Klinik II m.S. Onkologie und Hämatologie, Charité, Humboldt Universität, Berlin, Germany.
Fleischmann
Jessika
J
Klima
Kai-Michael
KM
Radonić
Aleksandar
A
Thulke
Stefanie
S
Siegert
Wolfgang
W
D018952:Antigens, CD34 / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D005312:Fetal Blood / Q000166:cytology* / Q000378:metabolism / Q000821:virology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000821:virology*
D018952:Antigens, CD34