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A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

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Cells are fused by MPMVE particles. (A) MPMVE must be continuously present in the medium to induce fusion. MPMVE was added to I0 cells, and the fused cells were scored at the indicated times (top, curve indicated with filled circles). Alternatively, MPMVE was added to one of the fusion partners for the indicated time, after which the cells were washed three times to remove unbound MPMVE, and the second fusion partner was added and the fused cells scored 16 h later (bottom, curve indicated with filled triangles). (B) The infection and fusion efficiencies of MPMVE do not correlate. Various amounts of MPMVE were added to the fusion assay with I0 cells, which were then incubated for 16 h to score fused cells or for 4 d to score for reverse transcriptase (RT) activity in tissue culture medium. The data are from three independent experiments, and the error bars indicate SD.
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fig6: Cells are fused by MPMVE particles. (A) MPMVE must be continuously present in the medium to induce fusion. MPMVE was added to I0 cells, and the fused cells were scored at the indicated times (top, curve indicated with filled circles). Alternatively, MPMVE was added to one of the fusion partners for the indicated time, after which the cells were washed three times to remove unbound MPMVE, and the second fusion partner was added and the fused cells scored 16 h later (bottom, curve indicated with filled triangles). (B) The infection and fusion efficiencies of MPMVE do not correlate. Various amounts of MPMVE were added to the fusion assay with I0 cells, which were then incubated for 16 h to score fused cells or for 4 d to score for reverse transcriptase (RT) activity in tissue culture medium. The data are from three independent experiments, and the error bars indicate SD.

Mentions: Cells can be fused by proteins of the viral particles, which does not require infection, or by viral proteins that are expressed in the infected cells. Several observations indicated that cell fusion induced by MPMVE did not require infection. MPMVE had to be continuously present in the medium to induce cell fusion (Fig. 6 A), which implies that fusion was directly caused by the added viral particles. Cell fusion was detectable within hours (Fig. 6 A), as opposed to the days required to express MPMV proteins (Fine et al., 1979), which is consistent with the finding that fused cells have no detectable MPMV proteins (Fig. S2 A, available at http://www.jcb.org/cgi/content/full/jcb.200507069/DC1). Azidothymidine, a reverse transcriptase inhibitor, prevented infection but not fusion (Fig. S2 B). Finally, the efficiencies of cell fusion and productive infection were unrelated (Fig. 6 B), confirming that fusion of the virus to the cells and fusion of cells induced by viruses or viruslike particles can be different processes (Schmid et al., 2000) and suggesting that hybrids produced by viruses may have no trace of the virus that created them, meaning that their viral etiology would be impossible to determine.


A primate virus generates transformed human cells by fusion.

Duelli DM, Hearn S, Myers MP, Lazebnik Y - J. Cell Biol. (2005)

Cells are fused by MPMVE particles. (A) MPMVE must be continuously present in the medium to induce fusion. MPMVE was added to I0 cells, and the fused cells were scored at the indicated times (top, curve indicated with filled circles). Alternatively, MPMVE was added to one of the fusion partners for the indicated time, after which the cells were washed three times to remove unbound MPMVE, and the second fusion partner was added and the fused cells scored 16 h later (bottom, curve indicated with filled triangles). (B) The infection and fusion efficiencies of MPMVE do not correlate. Various amounts of MPMVE were added to the fusion assay with I0 cells, which were then incubated for 16 h to score fused cells or for 4 d to score for reverse transcriptase (RT) activity in tissue culture medium. The data are from three independent experiments, and the error bars indicate SD.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2171256&req=5

fig6: Cells are fused by MPMVE particles. (A) MPMVE must be continuously present in the medium to induce fusion. MPMVE was added to I0 cells, and the fused cells were scored at the indicated times (top, curve indicated with filled circles). Alternatively, MPMVE was added to one of the fusion partners for the indicated time, after which the cells were washed three times to remove unbound MPMVE, and the second fusion partner was added and the fused cells scored 16 h later (bottom, curve indicated with filled triangles). (B) The infection and fusion efficiencies of MPMVE do not correlate. Various amounts of MPMVE were added to the fusion assay with I0 cells, which were then incubated for 16 h to score fused cells or for 4 d to score for reverse transcriptase (RT) activity in tissue culture medium. The data are from three independent experiments, and the error bars indicate SD.
Mentions: Cells can be fused by proteins of the viral particles, which does not require infection, or by viral proteins that are expressed in the infected cells. Several observations indicated that cell fusion induced by MPMVE did not require infection. MPMVE had to be continuously present in the medium to induce cell fusion (Fig. 6 A), which implies that fusion was directly caused by the added viral particles. Cell fusion was detectable within hours (Fig. 6 A), as opposed to the days required to express MPMV proteins (Fine et al., 1979), which is consistent with the finding that fused cells have no detectable MPMV proteins (Fig. S2 A, available at http://www.jcb.org/cgi/content/full/jcb.200507069/DC1). Azidothymidine, a reverse transcriptase inhibitor, prevented infection but not fusion (Fig. S2 B). Finally, the efficiencies of cell fusion and productive infection were unrelated (Fig. 6 B), confirming that fusion of the virus to the cells and fusion of cells induced by viruses or viruslike particles can be different processes (Schmid et al., 2000) and suggesting that hybrids produced by viruses may have no trace of the virus that created them, meaning that their viral etiology would be impossible to determine.

Bottom Line: Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability.We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die.Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

View Article: PubMed Central - PubMed

Affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

ABSTRACT
Amodel that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells.

Show MeSH
Related in: MedlinePlus