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Published on: July 28, 2016
Premature processing of mouse mammary tumor virus Gag polyprotein impairs intracellular capsid assembly
Ales Zábranský1, Romana Hadravová, Jitka Stokrová
1Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6, Czech Republic. ales@uochb.cas.cz
Abstract:
Mouse mammary tumor virus (MMTV) is the prototypical member of the Betaretrovirus genus, but the processes of its morphogenesis are poorly characterized. In this report, we describe an unusual intracellular processing of MMTV Gag polyprotein in human 293T cells transiently expressing MMTV from heterologous promoter. The same specific cleavage products of the viral protease were seen for the wild type as well as for nonmyristylated mutant of MMTV Gag polyprotein completely defective in the particle release. Inactivation of the viral protease resulted in more stable Gag polyprotein and in accumulation of intracytoplasmic particles for nonmyristylated Gag. The intracellular processing of nonmyristylated MMTV Gag indicates that protease activation in betaretrovirus can occur independently of budding.
Insights
This study reveals that Mouse Mammary Tumor Virus (MMTV) Gag polyprotein processing occurs within cells, independent of particle release. MMTV protease activation can happen before budding, offering new insights into betaretrovirus morphogenesis.
Area of Science:
- Virology
- Molecular Biology
- Cell Biology
Background:
- Mouse mammary tumor virus (MMTV) is a Betaretrovirus with poorly understood morphogenesis.
- Understanding MMTV Gag polyprotein processing is crucial for betaretrovirus replication insights.
Purpose of the Study:
- To investigate the intracellular processing of MMTV Gag polyprotein.
- To determine if MMTV protease activation is linked to particle release and budding.
Main Methods:
- Transient expression of MMTV in human 293T cells.
- Analysis of wild-type and nonmyristylated MMTV Gag polyprotein mutants.
- Assessment of viral protease activity and Gag polyprotein stability.
Main Results:
- Specific MMTV Gag polyprotein cleavage products were observed, indicating protease activity.
- A nonmyristylated MMTV Gag mutant, defective in particle release, still showed protease-mediated processing.
- Inactivating the MMTV protease led to Gag stabilization and intracytoplasmic particle accumulation.
Conclusions:
- MMTV Gag polyprotein processing occurs intracellularly.
- Betaretrovirus protease activation is independent of the viral budding process.
- This finding advances the understanding of MMTV assembly and betaretrovirus replication.
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