title: Parvovirus LuIII transducing vectors packaged by LuIII versus FPV capsid proteins: the VP1 N-terminal region is not a major determinant of human cell permissiveness.
abstract: Human cell lines are permissive for LuIII, a member of the rodent group of autonomous parvoviruses. However, LuIII vectors pseudotyped with feline panleukopaenia virus (FPV) capsid proteins can transduce feline cells but not human cells. Feline transferrin receptor (FelTfR) functions as a receptor for FPV. Transfection of Rh18A, a human rhabdomyosarcoma cell line, with FelTfR enabled transduction by vector with FPV capsid. This was not true of other human lines, suggesting restriction at some additional, post-entry, level(s) in human cells other than Rh18A. It seemed a reasonable hypothesis that a second blockage might be in nuclear delivery mediated by the N-terminal region of the minor capsid protein, VP1. We therefore generated virions containing an LuIII-luciferase genome, packaged using chimaeric VP1 molecules (N-terminal region of LuIII VP1, fused with body of FPV, and vice versa) together with the major capsid protein, VP2, of FPV or LuIII. The virions were tested for ability to transduce feline and human cells. Our hypothesis predicted that the N-terminal region of LuIII VP1 should allow transduction of human cells expressing FelTfR, while the FPV N-terminal region should not allow transduction of human cells (except for Rh18A). The experimental results did not bear out either of these predictions. Therefore, the VP1 N-terminal region appears not to be a major determinant of permissiveness for LuIII, versus FPV, capsid in human cells.
authors.affiliation: Department of Dermatology and University of Colorado Cancer Center, Health Sciences Center, Denver, CO 80262, USA.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Maxwell
authors.affiliation: Department of Dermatology and University of Colorado Cancer Center, Health Sciences Center, Denver, CO 80262, USA.
authors.forename: Françoise
authors.initials: F
authors.lastname: Maxwell
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D028301:Feline Panleukopenia Virus / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D017992:Parvovirus / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity; D014161:Transduction, Genetic
chemical_list: D036022:Capsid Proteins