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Secretion of a murine retroviral Env associated with resistance to infection
A Nihrane1, I Lebedeva, M S Lyu
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Abstract:
Fv4 is an endogenous defective murine leukaemia virus (MuLV) which expresses high levels of an envelope protein (Env) closely related to that of the ecotropic class of MuLVs. Mice bearing the natural Fv4 gene or a transgenic version are resistant to infection by ecotropic MuLVs. Fv4 mice secrete the surface peptide (SU) of the Fv4 Env in their serum and this secreted Env can block infection of NIH3T3 cells. To study the secretion of Fv4, we metabolically labelled cells expressing Fv4 Env or Env from infectious MuLVs and followed synthesis, glycosylation, proteolytic processing and secretion of Env species. We found no difference in the kinetics of synthesis or processing of Fv4 Env compared to the envelopes of infectious MuLVs, but Fv4 Env associated more weakly with its transmembrane anchor and was shed from the surface of cells.
Insights
Fv4, a defective murine leukemia virus (MuLV) envelope protein, is shed from cells. This shed Fv4 protein confers resistance to ecotropic MuLV infection in mice.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Fv4 is a defective murine leukemia virus (MuLV) encoding an envelope protein (Env) similar to ecotropic MuLVs.
- Mice with the Fv4 gene resist ecotropic MuLV infection, with secreted Fv4 Env blocking infection of NIH3T3 cells.
Purpose of the Study:
- To investigate the mechanism of Fv4 Env secretion.
- To compare the processing and secretion of Fv4 Env with infectious MuLV Env.
Main Methods:
- Metabolic labeling of cells expressing Fv4 Env or infectious MuLV Env.
- Analysis of Env synthesis, glycosylation, proteolytic processing, and secretion.
Main Results:
- Fv4 Env and infectious MuLV Env showed similar synthesis and processing kinetics.
- Fv4 Env exhibited weaker association with its transmembrane anchor, leading to shedding from cell surfaces.
Conclusions:
- The shedding of Fv4 Env from cell surfaces is a key mechanism for conferring resistance to ecotropic MuLV infection.
- Understanding Fv4 Env shedding provides insights into viral interference mechanisms.