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Efficient cell infection by Moloney murine leukemia virus-derived particles requires minimal amounts of envelope
E Bachrach1, M Marin, M Pelegrin
1Institut de Génétique Moléculaire, UMR 5535/IFR24, CNRS, BP 5051, 34293 Montpellier Cedex 05, France.
Abstract:
Retrovirus entry into cells is mediated by specific interactions between the retrovirally encoded Env envelope glycoprotein and a host cell surface receptor. Though a number of peptide motifs responsible for the structure as well as for the binding and fusion activities of Env have been identified, only a few quantitative data concerning the infection process are available. Using an inducible expression system, we have expressed various amounts of ecotropic and amphotropic Env at the surfaces of Moloney murine leukemia virus-derived vectors and assayed for the infectivity of viral particles. Contrary to the current view that numerous noncooperative Env-viral receptor interactions are required for cell infection, we report here that very small amounts of Env are sufficient for optimal infection. However, increasing Env density clearly accelerates the rate at which infectious attachment to cells occurs. Moreover, our data also show that a surprisingly small number of Env molecules are sufficient to drive infection, albeit at a reduced efficiency, and that, under conditions of low expression, Env molecules act cooperatively. These observations have important consequences for our understanding of natural retroviral infection as well as for the design of cell-targeted infection techniques involving retroviral vectors.
Insights
Very small amounts of retroviral Env envelope glycoproteins are sufficient for optimal cell infection. Increasing Env density accelerates infection rates, and low Env expression shows cooperative binding, impacting retroviral vector design.
Area of Science:
- Virology
- Molecular Biology
- Biophysics
Background:
- Retrovirus cell entry relies on Env envelope glycoproteins binding to host receptors.
- Quantitative data on Env-mediated infection dynamics are limited.
- Existing models suggest numerous Env-receptor interactions are necessary for infection.
Purpose of the Study:
- To investigate the quantitative relationship between Env expression levels and retroviral infectivity.
- To determine the minimum Env requirement for efficient viral entry.
- To explore the cooperative behavior of Env molecules during infection.
Main Methods:
- Utilized an inducible expression system to control Env levels on Moloney murine leukemia virus-derived vectors.
- Quantified viral particle infectivity across a range of ecotropic and amphotropic Env surface densities.
- Assayed Env-receptor interaction dynamics under varying Env expression conditions.
Main Results:
- Minimal Env expression levels are sufficient for achieving optimal retroviral infection.
- Higher Env density significantly enhances the rate of infectious cell attachment.
- Low Env expression demonstrates cooperative Env molecule action, albeit with reduced efficiency.
Conclusions:
- The findings challenge the prevailing view of noncooperative Env-receptor interactions.
- A small number of Env molecules can mediate infection, suggesting cooperative mechanisms are key.
- These insights are crucial for understanding natural retroviral infections and designing targeted retroviral vectors.