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The role of envelope glycoprotein processing in murine leukemia virus infection
Abstract:
The murine leukemia virus envelope protein is synthesized as a precursor molecule, Pr85env, which is proteolytically cleaved at an arginine residue to produce two mature envelope proteins, gp70 and p15(E). The results presented here indicate that mutation to lysine of the arginine found at the envelope precursor cleavage site results in a precursor which is cleaved with an efficiency at least 10-fold lower than the efficiency with which the wild-type protein is cleaved. This mutation has been used to investigate the requirement for envelope protein processing in various aspects of retroviral infection. Viruses produced by cells transfected with mutant proviral clones are approximately 10-fold less infectious than wild-type viruses. Mutant viruses are incapable of inducing XC cell syncytium formation and are 100-fold less efficient than wild-type viruses at rendering cells resistant to superinfection. Envelope glycoproteins bearing the lysine mutation are found in reduced amounts on the surface of infected cells, and as a result mutant virions contain significantly less envelope protein than do wild-type virions. The phenotypic effects of the processing mutation described here are most likely the result of this paucity of envelope glycoproteins in virions carrying the mutation.
Insights
Altering the murine leukemia virus envelope precursor cleavage site reduces viral infectivity. This mutation significantly impairs envelope protein processing, leading to less infectious and less potent retroviruses.
Area of Science:
- Retroviral biology
- Molecular virology
- Protein processing
Background:
- Murine leukemia virus envelope protein (Pr85env) is cleaved into mature gp70 and p15(E) at an arginine residue.
- Envelope protein processing is crucial for retroviral infectivity and function.
Purpose of the Study:
- To investigate the role of envelope precursor cleavage in murine leukemia virus infection.
- To analyze the impact of a specific cleavage site mutation on viral properties.
Main Methods:
- Site-directed mutagenesis of the arginine cleavage site to lysine in the envelope precursor.
- Analysis of viral infectivity, syncytium formation, and superinfection resistance.
- Quantification of envelope glycoproteins on infected cells and virions.
Main Results:
- Mutation to lysine reduced cleavage efficiency by at least 10-fold compared to wild-type.
- Mutant viruses showed a 10-fold decrease in infectivity and 100-fold decrease in superinfection resistance.
- Reduced envelope glycoproteins on mutant virions correlated with impaired viral functions.
Conclusions:
- Envelope precursor cleavage is essential for efficient murine leukemia virus infection.
- The paucity of envelope glycoproteins due to impaired processing significantly affects viral infectivity and cell resistance.
- This study highlights the critical role of post-translational modification in retroviral pathogenesis.