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 c ells exposed to virus-containing supernatants from ecotropic retroviral hel per cells occasionally fused to neighboring cells, resulting in syncytia (g iant cells with multiple nuclei). Polycationic molecules dramatically enhan ced the effect, leading to widespread cell death. The degree of cell fusion was dependent upon the retroviral envelope subtype (ecotropic-->amphotropi c, gibbon ape leukemia virus was negative) as well as on the polycationic r eagent used (G9 dendrimer-->Lipofectamine-->polybrene). Cell fusion effects were not mediated by the retroviral vector backbone, because virus-contain ing supernatants from helper cells (without vector) and vector producer cel ls had a similar effect. Human target cells were not fused by any type of m urine retrovirus; in addition, amphotropic virus from human helper cells wa s 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.