Retrovirus-induced Cell Fusion Is Enhanced by Protease Treatment

Andersen, Klaus B.; Skov, H.

doi:10.1099/0022-1317-70-7-1921

Cited by 30 publications

(21 citation statements)

References 21 publications

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“…Furthermore, these basic amino acids are likely to occur on the surface of the protein (Birdi, 1989). We have previously shown that cleavage of gp70 might be important for membrane fusion and infection (Andersen, 1987;Andersen & Skov, 1989). Similar results have been indicated for HIV gpl20 (Clement et al, 1991 putative cleavage may be caused by a trypsin-like protease as infection can be inhibited by leupeptin and antipain (Andersen, 1983).…”

Section: Introductionsupporting

confidence: 64%

Mutational analysis of Moloney murine leukaemia virus surface protein gp70

Skov

Andersen

1993

Journal of General Virology

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Ten mutations were generated in the env gene of Moloney murine leukaemia virus DNA. The mutations were made by site-directed mutagenesis to alter basic amino acids (lysine or arginine) in the surface glycoprotein gp70. Mutants were investigated following transfection into NIH/3T3 cells. All 10 mutants released virion particles into the medium, suggesting that none of the mutations affected overall viral gene expression or virion budding. Two mutants were positive in XC plaque assay, reverse transcriptase assay and re-infection experiments, showing that these mutations occurred in parts of the molecule not essential for infection. Three mutants were negative in both the XC plaque assay and re-infection experiments, suggesting that they make noninfectious virus particles. The results indicate a defect in the early phase of infection, perhaps in receptor binding or in the fusion ofvirion and host membranes. The other mutations resulted in reduced infectivity of released virion particles.

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Section: Introductionsupporting

confidence: 64%

Mutational analysis of Moloney murine leukaemia virus surface protein gp70

Skov

Andersen

1993

Journal of General Virology

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“…Host cell-determined routes of virus entry have not been observed for other enveloped viruses, in which the pH dependence is solely a property of the viral envelope glycoproteins. One explanation for the unusual phenomenon with XC cells might be the expression of a cell surface proteinase able to cleave the gp70 glycoprotein of MLV-E. Andersen (1985Andersen ( , 1987 has reported that gp70 is cleaved during MLV-E entry, and that MLV-Einduced cell fusion is enhanced by exogenous proteinase treatment (Andersen & Skov, 1989). It is likely that gp70 cleavage is a required post-adsorption step in the entry of MLV-E into cells (Andersen & Skov, 1989).…”

Section: Discussionmentioning

confidence: 99%

“…One explanation for the unusual phenomenon with XC cells might be the expression of a cell surface proteinase able to cleave the gp70 glycoprotein of MLV-E. Andersen (1985Andersen ( , 1987 has reported that gp70 is cleaved during MLV-E entry, and that MLV-Einduced cell fusion is enhanced by exogenous proteinase treatment (Andersen & Skov, 1989). It is likely that gp70 cleavage is a required post-adsorption step in the entry of MLV-E into cells (Andersen & Skov, 1989). In that case, one could postulate that the activity of the proteinases that cleave MLV gp70 normally may be dependent on the low pH of endosomes in most cells, and hence is sensitive to weak bases such as NH~CI.…”

Section: Discussionmentioning

confidence: 99%

The pH independence of mammalian retrovirus infection

McClure

Sommerfelt

Marsh

et al. 1990

Journal of General Virology

199

225

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The pH dependence of early steps in the infection of human and other cells by mammalian retroviruses and retroviral pseudotype particles of vesicular stomatitis virus (VSV) was investigated for 10 strains of retrovirus, including C-type and D-type oncoviruses and human lentiviruses. When cells were treated with weak bases (NH4CI and amantadine) to raise the pH of endocytic vesicles, only ecotropic murine leukaemia virus (MLV-E) and VSV showed pH-dependent entry. Pretreatment of retrovirus stocks in media below pH 5.0 did not reduce their titres but inactivated VSV to < 10 -8 of the initial titre. VSV(MLV-E) pseudotype infection in five out of six mouse and rat cell lines was inhibited by NH4CI, indicating that infection proceeds via receptor-mediated endocytosis. In contrast, NH4C1 treatment has no effect on the infection of XC cells in which MLV-E induces syncytia. It is postulated that the pH-independent entry and cell fusion of XC cells by MLV-E may result from the activity of a cell surface proteinase that cleaves viral gp70 at neutral pH.

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“…The transition of immature TM to its fusogenic form involves proteolytic cleavage of 16 amino acid residues at the carboxyl terminus of TM, or glycoprotein 15, to a truncated and active glycoprotein 12. The fusion process of various retroviruses is reportedly affected by changes in pH, 9 protease activity, 10 and amphotericin B, 11 or by growth in murine XC cells. 12 The ability of cells to survive retroviral infections is apparently facilitated by the controlled maturation of wild-type TM after the virus leaves the cell.…”

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confidence: 99%

Fusogenic effects of murine retroviruses and cationic enhancers of transduction

Solaiman

Zink

et al. 2000

Cancer Gene Ther

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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 (ecotropic3amphotropic, gibbon ape leukemia virus was negative) as well as on the polycationic reagent used (G9 dendrimer3 Lipofectamine3polybrene). 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. Cancer Gene Therapy (2000) 7, 53-58

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Retrovirus-induced Cell Fusion Is Enhanced by Protease Treatment

Abstract: SUMMARYThe effect of proteases on retrovirus-induced cell fusion was studied. Both 'fusion from within' (fusion between infected and uninfected cells) and 'fusion from without' (fusion of uninfected cells by virus addition) was enhanced after treatment with proteases.

Cited by 30 publications

References 21 publications

Mutational analysis of Moloney murine leukaemia virus surface protein gp70

Mutational analysis of Moloney murine leukaemia virus surface protein gp70

The pH independence of mammalian retrovirus infection

Fusogenic effects of murine retroviruses and cationic enhancers of transduction

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