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Fusion between uninfected cells in retrovirus-induced fusion-from-within
1Department of Pharmacology, Royal Danish School of Pharmacy, Copenhagen. kba@mail.dfh.dk
Abstract:
We previously examined Moloney murine leukemia virus-induced fusion-from-within (FFWI) and fusion-from-without (FFWO) of SC-1 mouse cells. FFWI and FFWO can be distinguished by their stimulation by ionophores and polycations, respectively. FFWI is caused by infected cells. Normally, fusion between an infected cell and uninfected cells (heterofusions) is described, but we have surprisingly found that the infected cells also caused homofusion between uninfected cells in their vicinity (named neighbor homofusions). It was shown that neighbor homofusions were not induced by free virus particles (by FFWO). Transfectants expressing envelope proteins only induced heterofusions, indicating that virus production is necessary for the formation of neighbor homofusions. Both plasma membrane fragments and easily removable material from the surface of infected cells were able to induce fusion with the same stimulation pattern as FFWI and neighbor homofusion. These materials, especially the latter, have properties in common with virions, and it is discussed whether immature virions are involved in the formation of the neighbor homofusions.
Insights
Moloney murine leukemia virus causes cell fusion. Infected cells induce fusion in neighboring uninfected cells (neighbor homofusions), a process requiring virus production and potentially immature virions.
Area of Science:
- Virology
- Cell Biology
- Membrane Fusion
Background:
- Moloney murine leukemia virus (MMLV) induces cell-to-cell fusion.
- Previously studied fusion mechanisms include fusion-from-within (FFWI) and fusion-from-without (FFWO).
- FFWI is ionophore-stimulated, while FFWO is polycation-stimulated.
Purpose of the Study:
- To investigate novel fusion mechanisms induced by MMLV-infected cells.
- To differentiate between virus-mediated and cell-mediated fusion events.
- To explore the role of viral components in MMLV-induced cell fusion.
Main Methods:
- Co-culture of MMLV-infected SC-1 cells with uninfected SC-1 cells.
- Analysis of fusion events, distinguishing heterofusions and homofusions.
- Experimental manipulation using ionophores, polycations, and transfectants expressing viral envelope proteins.
- Characterization of cell surface materials capable of inducing fusion.
Main Results:
- MMLV-infected cells induced homofusion in neighboring uninfected cells (neighbor homofusions).
- Neighbor homofusions were not induced by free virus particles (FFWO).
- Virus production, not just envelope proteins, is necessary for neighbor homofusions.
- Plasma membrane fragments and surface-associated material from infected cells induced fusion with FFWI/neighbor homofusion patterns.
- These materials share properties with virions, suggesting a role for immature virions.
Conclusions:
- MMLV-infected cells mediate a novel homofusion process in adjacent uninfected cells.
- This neighbor homofusion requires active virus production and is distinct from FFWO.
- Immature virions or related surface components are implicated in the observed homofusion events.