title: Fc receptor-mediated, antibody-dependent enhancement of bacteriophage lambda-mediated gene transfer in mammalian cells.
abstract: Lambda phage vectors mediate gene transfer in cultured mammalian cells and in live mice, and in vivo phage-mediated gene expression is increased when mice are pre-immunized with bacteriophage lambda. We now show that, like eukaryotic viruses, bacteriophage vectors are subject to Fc receptor-mediated, antibody-dependent enhancement of infection in mammalian cells. Antibody-dependent enhancement of phage gene transfer required FcgammaRI, but not its associated gamma-chain, and was not supported by other FcgammaR family members (FcgammaRIIA, FcgammaRIIB, and FcgammaRIII). Studies using chlorpromazine and latrunculin A revealed an important role for clathrin-mediated endocytosis (chlorpromazine) and actin filaments (latrunculin A) in antibody-enhanced phage gene transfer. This was confirmed by experiments using inhibitors of endosomal acidification (bafilomycin A1, monensin) and by immunocytochemical colocalization of internalized phage particles with early endosome-associated protein-1 (EAA1). In contrast, microtubule-targeting agents (nocodazole, taxol) increased the efficiency of antibody-enhanced phage gene transfer. These results reveal an unexpected antibody-dependent, FcgammaRI-mediated enhancement of phage transduction in mammalian cells, and suggest new approaches to improve bacteriophage-mediated gene transfer.
authors.affiliation: Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, USA.
authors.forename: Ramil
authors.initials: R
authors.lastname: Sapinoro
authors.forename: Ketna
authors.initials: K
authors.lastname: Volcy
authors.forename: W W Shanaka I
authors.initials: WW
authors.lastname: Rodrigo
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Schlesinger
authors.forename: Stephen
authors.initials: S
authors.lastname: Dewhurst
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000008:administration & dosage*; D010582:Bacteriophage lambda / Q000235:genetics* / Q000276:immunology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D019556:COS Cells; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D002746:Chlorpromazine / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects; D018014:Gene Transfer Techniques; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D008156:Luciferases / Q000235:genetics; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D000199:Actins; D000914:Antibodies, Viral; D019086:Bridged Bicyclo Compounds, Heterocyclic; D036022:Capsid Proteins; D006023:Glycoproteins; D017452:Receptors, IgG; D011994:Recombinant Proteins; D053778:Thiazolidines; C406073:gpD protein, lambda phage; D008156:Luciferases; D017239:Paclitaxel; D015739:Nocodazole; C037067:latrunculin A; D002746:Chlorpromazine