Targeting and hematopoietic suppression of human CD34+ cells by measles virus.
The major cause of mortality in measles is generalized suppression of cell-mediated immunity that persists following virus clearance and results in secondary infections. The mechanisms contributing to this long-term immunosuppression are not clear. Herein we present evidence that measles virus (MV) disrupts hematopoiesis by infecting human CD34+ cells and human bone marrow stroma. MV infection does not affect the hematopoietic capability of hematopoietic stem cells (HSCs) directly; rather, the infection impairs the ability of stroma to support development of HSCs. These results suggest that MV-mediated defects in hematopoiesis contribute to the long-term immunosuppression seen in measles.
Manchester
Marianne
M
Departments of Cell Biology, Center for Integrative Molecular Biosciences, The Scripps Research Institute, 10550 N Torrey Pines Road, La Jolla, CA 92037, USA. marim@scripps.edu
Smith
Kent A
KA
Eto
Danelle S
DS
Perkin
Hugh B
HB
Torbett
Bruce E
BE
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000032:analysis*; D001854:Bone Marrow Cells / Q000502:physiology / Q000821:virology*; D002460:Cell Line; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology / Q000821:virology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology / Q000821:virology*; D006801:Humans; D007165:Immunosuppression Therapy; D008457:Measles / Q000276:immunology / Q000503:physiopathology* / Q000821:virology*; D008459:Measles virus / Q000502:physiology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011991:Receptors, Virus / Q000032:analysis; D017154:Stromal Cells / Q000821:virology
D015703:Antigens, CD; D018952:Antigens, CD34; C497857:CD46 protein, human; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D011991:Receptors, Virus