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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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Fusogenicity is associated with an exosome-like virus. (A and B) Exosomes were fractionated by sedimentation in a velocity gradient (see Materials and methods), and aliquots of the fractions were analyzed in the fusion assay with I0 cells (A) or reverse transcriptase activity (B). The insets in A show an electron micrograph of fraction 7 and the content of CD81 in the fractions analyzed by dot blotting. The inset in B compares the reverse transcriptase activity in P70 from I0 and IEH cells. (C) The fractions obtained in A were analyzed by electrophoresis and the indicated polypeptides by mass spectrometry (Table S2). The data in A and in the inset in B are from three independent experiments, and the data in B are the mean of two independent experiments. The error bars indicate SD.
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fig3: Fusogenicity is associated with an exosome-like virus. (A and B) Exosomes were fractionated by sedimentation in a velocity gradient (see Materials and methods), and aliquots of the fractions were analyzed in the fusion assay with I0 cells (A) or reverse transcriptase activity (B). The insets in A show an electron micrograph of fraction 7 and the content of CD81 in the fractions analyzed by dot blotting. The inset in B compares the reverse transcriptase activity in P70 from I0 and IEH cells. (C) The fractions obtained in A were analyzed by electrophoresis and the indicated polypeptides by mass spectrometry (Table S2). The data in A and in the inset in B are from three independent experiments, and the data in B are the mean of two independent experiments. The error bars indicate SD.

Mentions: A possible difference was suggested by the Trojan exosome hypothesis, which states that retroviruses, many of which are fusogenic, can be released in exosomes. Using this mechanism, the virus may expand its host range by using cellular proteins incorporated in its membrane to facilitate fusion and to avoid immune surveillance (Gould et al., 2003). Therefore, we repeated the mass spectrometry analysis, this time using total lysates of purified exosomes (Fig. 3 A). Major polypeptides recovered from the fractions with fusogenic activity (fraction 7; Fig. 3, A and C) were encoded by the Mason-Pfizer monkey virus (MPMV; Table S2, available at http://www.jcb.org/cgi/content/full/jcb.200507069/DC1; for review see Fine and Schochetman, 1978), suggesting that exosomes carried this virus.


A primate virus generates transformed human cells by fusion.

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

Fusogenicity is associated with an exosome-like virus. (A and B) Exosomes were fractionated by sedimentation in a velocity gradient (see Materials and methods), and aliquots of the fractions were analyzed in the fusion assay with I0 cells (A) or reverse transcriptase activity (B). The insets in A show an electron micrograph of fraction 7 and the content of CD81 in the fractions analyzed by dot blotting. The inset in B compares the reverse transcriptase activity in P70 from I0 and IEH cells. (C) The fractions obtained in A were analyzed by electrophoresis and the indicated polypeptides by mass spectrometry (Table S2). The data in A and in the inset in B are from three independent experiments, and the data in B are the mean of two independent experiments. The error bars indicate SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171256&req=5

fig3: Fusogenicity is associated with an exosome-like virus. (A and B) Exosomes were fractionated by sedimentation in a velocity gradient (see Materials and methods), and aliquots of the fractions were analyzed in the fusion assay with I0 cells (A) or reverse transcriptase activity (B). The insets in A show an electron micrograph of fraction 7 and the content of CD81 in the fractions analyzed by dot blotting. The inset in B compares the reverse transcriptase activity in P70 from I0 and IEH cells. (C) The fractions obtained in A were analyzed by electrophoresis and the indicated polypeptides by mass spectrometry (Table S2). The data in A and in the inset in B are from three independent experiments, and the data in B are the mean of two independent experiments. The error bars indicate SD.
Mentions: A possible difference was suggested by the Trojan exosome hypothesis, which states that retroviruses, many of which are fusogenic, can be released in exosomes. Using this mechanism, the virus may expand its host range by using cellular proteins incorporated in its membrane to facilitate fusion and to avoid immune surveillance (Gould et al., 2003). Therefore, we repeated the mass spectrometry analysis, this time using total lysates of purified exosomes (Fig. 3 A). Major polypeptides recovered from the fractions with fusogenic activity (fraction 7; Fig. 3, A and C) were encoded by the Mason-Pfizer monkey virus (MPMV; Table S2, available at http://www.jcb.org/cgi/content/full/jcb.200507069/DC1; for review see Fine and Schochetman, 1978), suggesting that exosomes carried this virus.

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