Fusogenic effects of murine retroviruses and cationic enhancers of transduction.
The maturation of retrovirus particles involves proteolytic cleavage of the envelope glycoprotein transmembrane component, resulting in conversion of the virus particle to a fusogenic or infectious state. Susceptible murine cells exposed to virus-containing supernatants from ecotropic retroviral helper cells occasionally fused to neighboring cells, resulting in syncytia (giant cells with multiple nuclei). Polycationic molecules dramatically enhanced the effect, leading to widespread cell death. The degree of cell fusion was dependent upon the retroviral envelope subtype (ecotropic-->amphotropic, gibbon ape leukemia virus was negative) as well as on the polycationic reagent used (G9 dendrimer-->Lipofectamine-->polybrene). Cell fusion effects were not mediated by the retroviral vector backbone, because virus-containing supernatants from helper cells (without vector) and vector producer cells had a similar effect. Human target cells were not fused by any type of murine retrovirus; in addition, amphotropic virus from human helper cells was not fusogenic toward murine cells. Thus, fusogenic effects were important during the propagation of vectors using murine helper cells but were not a significant factor during the transduction of human cells.
Xu
G
G
Creighton Cancer Center/Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Solaiman
F
F
Zink
M A
MA
Hodgson
C P
CP
D016475:3T3 Cells; D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology; D002412:Cations / Q000494:pharmacology*; D002459:Cell Fusion; D002478:Cells, Cultured; D003428:Cross Infection / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D015316:Genetic Therapy / Q000379:methods; D015726:Giant Cells / Q000821:virology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D012190:Retroviridae / Q000235:genetics / Q000472:pathogenicity*; D014161:Transduction, Genetic / Q000235:genetics; D014771:Virion / Q000187:drug effects / Q000472:pathogenicity; D019065:Virus Assembly
D001798:Blood Proteins; D002412:Cations