Human cytomegalovirus infection of bone marrow myofibroblasts enhances myeloid progenitor adhesion and elicits viral transmission.
Human cytomegalovirus (CMV) infection of bone marrow transplant recipients can cause pancytopenia, as well as life-threatening interstitial pneumonia. CMV replicates actively in bone marrow stromal cells, whereas it remains latent in hematopoietic progenitors. Our aim was to study the influence of CMV infection on adherence of CD34(+) cells to the myofibroblastic component of human bone marrow and examine transmission of virus from myofibroblasts to CD34(+) cells. We show that smooth actin, but not fibronectin, organization is markedly modified by CMV infection of bone marrow stromal myofibroblasts. Nonetheless, CMV infection led to increased adherence of the CD34(+) progenitor cell line, KG1a, relative to adherence to uninfected myofibroblasts from the same donors. Adherence of CD34(+) cells to infected bone marrow myofibroblasts resulted in transfer of virions and viral proteins through close cell-to-cell contacts. This phenomenon may play a role in the pathophysiology of CMV bone marrow infection and in eventual virus dissemination.
Michelson
S
S
Unité d'immunologie virale, Institut Pasteur, 28, rue du Dr. Roux, 75724 Paris cédex 15, Paris, France. michelso@wanadoo.fr
Rohrlich
P
P
Beisser
P
P
Laurent
L
L
Perret
E
E
Prévost
M C
MC
Monchatre
E
E
Duval
M
M
Marolleau
J P
JP
Charbord
P
P
D000199:Actins / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000821:virology*; D002448:Cell Adhesion; D002460:Cell Line; D003587:Cytomegalovirus / Q000472:pathogenicity*; D005353:Fibronectins / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000502:physiology* / Q000821:virology; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D017154:Stromal Cells / Q000821:virology; D014763:Viral Matrix Proteins / Q000378:metabolism; D014779:Virus Replication
D000199:Actins; D018952:Antigens, CD34; D005353:Fibronectins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa