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Requirements for mouse mammary tumour virus internalization in mouse mammary epithelial cells
1Department of Biological Sciences, University of South Carolina, Columbia 29208, USA. Bolander@Biol.SC. Edu
Abstract:
Methylamine, a lysosomotropic alkalinizing agent, blocked mouse mammary tumour virus (MMTV) infection in normal mouse mammary epithelium, suggesting that internalization and acidification are necessary for cell penetration. This mechanism was further supported by the fact that intact MMTV induced the translocation of its cellular binding protein from the plasmalemma to the microsomes; however, isolated gp52, the MMTV envelope protein that binds this receptor, did not redistribute the binding protein. These data suggest that either another viral component, in addition to gp52, is needed for cell entry or that internalization requires receptor aggregation, which only the multivalent viral envelope can induce.
Insights
Methylamine blocked mouse mammary tumour virus (MMTV) infection, indicating MMTV entry requires cell penetration and acidification. Intact MMTV, not just its envelope protein gp52, triggered cellular binding protein translocation, suggesting multivalent interactions are key for viral entry.
Area of Science:
- Virology
- Cell Biology
- Biochemistry
Background:
- Mouse mammary tumour virus (MMTV) is an oncogenic retrovirus.
- Viral entry into host cells is a critical step in infection.
- Understanding MMTV entry mechanisms is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the mechanism of MMTV cell entry.
- To determine the role of acidification and viral components in MMTV infection.
Main Methods:
- Treatment of normal mouse mammary epithelial cells with methylamine, a lysosomotropic agent.
- Analysis of MMTV infection rates.
- Tracking the translocation of the MMTV cellular binding protein using biochemical methods.
Main Results:
- Methylamine blocked MMTV infection, suggesting acidification is necessary for cell penetration.
- Intact MMTV induced the translocation of its cellular binding protein from the plasma membrane to microsomes.
- Isolated MMTV envelope protein gp52 did not induce this translocation.
Conclusions:
- MMTV entry into mammary epithelial cells requires internalization and acidification.
- Viral entry likely necessitates multivalent interactions mediated by the intact viral envelope, possibly involving receptor aggregation, in addition to the gp52 protein.