Factors involved in the sensitivity of different hematopoietic cell lines to infection by subgroup C adenovirus: implication for gene therapy of human lymphocytic malignancies.
Gene transfer approaches using viruses such human adenovirus (HAdV) may provide an alternative treatment for diseases involving hematopoietic cells. Better understanding of the cellular mechanisms by which the HAdV introduces DNA into these cells should help in vector design. We examined HAdV intracellular delivery in several cell lines including B and T lymphocytes. We demonstrated that HAdV resistance in most B lymphocytes is the result of moderate HAdV uptake. In contrast, high levels of coxsackie and HAdV receptor (hCAR) are expressed on the surface of HSB2 (T cells), allowing efficient binding and uptake but no transgene expression, probably because of deficient endosomolysis and subsequent exocytose. This work demonstrates the existence of hCAR-dependent and -independent endocytic route in hematopoietic cells. Moreover, it precises the intracellular barriers to be overcome by HAdV in such cells to be infectious and gives previous information's to design new vectors for gene transfer.
Colin
Morvane
M
INSERM U524, IMPRT, 1 place de Verdun, 59045 Lille Cedex, France. colin@lille.inserm.fr
Renaut
Laurence
L
Mailly
Laurent
L
D'Halluin
Jean-Claude
JC
D000256:Adenoviridae / Q000472:pathogenicity / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D040881:CD11a Antigen / Q000032:analysis; D018821:CD18 Antigens / Q000032:analysis; D002460:Cell Line; D045744:Cell Line, Tumor; D004705:Endocytosis; D005452:Fluoresceins; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000821:virology*; D006801:Humans; D011991:Receptors, Virus / Q000096:biosynthesis; D013045:Species Specificity; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D014779:Virus Replication; D001616:beta-Galactosidase / Q000235:genetics
D040881:CD11a Antigen; D018821:CD18 Antigens; D005452:Fluoresceins; D005456:Fluorescent Dyes; D011991:Receptors, Virus; C024098:6-carboxyfluorescein; D001616:beta-Galactosidase