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Analysis of Assembly and Budding of Lujo Virus
Shuzo Urata1, Jacqueline Weyer2, Nadia Storm2
1Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan.
Abstract:
The recently identified arenavirus Lujo virus (LUJV) causes fatal hemorrhagic fever in humans. We analyzed its mechanism of viral release driven by matrix protein Z and the cell surface glycoprotein precursor GPC. The L domains in Z are required for efficient virus-like particle release, but Tsg101, ALIX/AIP1, and Vps4A/B are unnecessary for budding. LUJV GPC is cleaved by site 1 protease (S1P) at the RKLM motif, and treatment with the S1P inhibitor PF-429242 reduced LUJV production.
Insights
Lujo virus (LUJV) release depends on matrix protein Z, but not on Tsg101, ALIX/AIP1, or Vps4A/B. Site 1 protease cleavage of LUJV glycoprotein precursor GPC is crucial for virus production.
Area of Science:
- Virology
- Molecular Biology
Background:
- Lujo virus (LUJV) is a recently identified arenavirus responsible for severe, often fatal, hemorrhagic fever in humans.
- Understanding the mechanisms of LUJV replication and release is critical for developing antiviral strategies.
Purpose of the Study:
- To elucidate the molecular mechanisms governing the release of Lujo virus from infected cells.
- To investigate the roles of the matrix protein Z and the glycoprotein precursor GPC in viral egress.
Main Methods:
- Analysis of virus-like particle release mediated by matrix protein Z.
- Assessment of the necessity of cellular factors like Tsg101, ALIX/AIP1, and Vps4A/B for LUJV budding.
- Investigation of the proteolytic cleavage of LUJV GPC by site 1 protease (S1P).
- Utilizing the S1P inhibitor PF-429242 to evaluate its impact on LUJV production.
Main Results:
- The L domains within the matrix protein Z are essential for efficient virus-like particle release.
- Key cellular proteins Tsg101, ALIX/AIP1, and Vps4A/B are not required for LUJV budding.
- LUJV GPC undergoes cleavage by S1P at the specific motif RKLM.
- Inhibition of S1P using PF-429242 significantly reduced the production of LUJV.
Conclusions:
- LUJV egress is primarily mediated by matrix protein Z through a pathway independent of canonical ESCRT machinery components.
- Proteolytic processing of GPC by S1P is a vital step in the LUJV life cycle, representing a potential therapeutic target.