Efficient species C HAdV infectivity in plasmocytic cell lines using a clathrin-independent lipid raft/caveola endocytic route.
Hematopoietic cells are known to be refractory to species C human adenovirus (HAdV) infection; however, the reason for this has not been clearly established. We have previously demonstrated that this nonpermissivity is the consequence of inefficient HAdV particle uptake, notably in B lymphocytes. We noted that while the protein clathrin is observed in association with membranes in epithelial cells, it is found predominantly in the cytoplasm of hematopoietic cell lines. So it appears that altered clathrin-coated pit endocytosis could explain the weak HAdV uptake in B cells. In contrast, mature B cell plasmocytes are permissive to HAdV. However, this is not the result of clathrin-coated pit endocytosis since this process is also inefficient in these cells. Confocal microscopy showed colocalization between HAdV particles and caveolae/lipid rafts in plasmocytes. Moreover, inhibiting caveola endocytosis by depletion of cholesterol or expression of dominant negative caveolin-1 in these cells results in a 50-70% reduction in HAdV infectivity. It appears that caveola endocytosis and nonclathrin noncaveola endocytosis are used by HAdV to enter plasmocytes in response to a loss of the clathrin-dependent pathway. Thus targeting of caveolae by modifying the capsid of HAdV may represent an alternative approach to enhancing uptake in most hematopoietic cells for future gene therapy.
Colin
Morvane
M
INSERM U524, IMPRT, Institut de Recherches sur le Cancer de Lille, 1 place de Verdun, 59045 Lille Cedex, France.
Mailly
L
L
Rogée
S
S
D'Halluin
Jean-Claude
JC
D000260:Adenoviruses, Human / Q000235:genetics* / Q000502:physiology*; D015703:Antigens, CD / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism; D004705:Endocytosis; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000235:genetics / Q000502:physiology; D006413:Hematopoietic System / Q000166:cytology; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism*; D010587:Phagocytosis; D011990:Receptors, Transferrin; D014168:Transferrin / Q000494:pharmacology; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C495540:CAV1 protein, human; C068126:CD71 antigen; D051242:Caveolin 1; D022461:Caveolins; D002966:Clathrin; D011990:Receptors, Transferrin; D014168:Transferrin; D001616:beta-Galactosidase