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The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies

Mar Perez1, Rebecca C Craven, Juan C de la Torre

  • 1Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 18, 2003
PubMed

Insights

The arenavirus Z protein drives virus budding, acting similarly to matrix proteins in other viruses. This discovery offers new avenues for antiviral strategies against hemorrhagic fever arenaviruses.

Area of Science:

  • Virology
  • Molecular Biology
  • Cell Biology

Background:

  • Arenaviruses, including Lymphocytic choriomeningitis virus (LCMV) and Lassa fever virus (LFV), are significant human pathogens.
  • Virus budding, a critical step in viral replication, is essential for the release of new virions.
  • The mechanisms governing arenavirus budding have not been fully elucidated.

Purpose of the Study:

  • To identify the key viral factor responsible for arenavirus budding.
  • To investigate the role of the small RING finger Z protein in the budding process.
  • To explore potential antiviral targets within the arenavirus budding pathway.

Main Methods:

  • Utilized a reverse genetics system based on Lymphocytic choriomeningitis virus (LCMV).
  • Employed mutational analysis of proline-rich motifs (PPPY, PTAP) within the Z protein.
  • Investigated the interaction of Z proteins with Tsg101, a component of the vacuolar protein sorting machinery.
  • Applied RNA interference to target Tsg101 expression.

Main Results:

  • Identified the arenavirus small RING finger Z protein as the primary driver of virus budding.
  • Demonstrated that both LCMV and LFV Z proteins exhibit self-budding activity and can substitute for retroviral late domains.
  • Showed that proline-rich motifs (PPPY, PTAP) in Z proteins are crucial for efficient budding.
  • Confirmed that Z proteins recruit Tsg101 to the plasma membrane, a process essential for budding.
  • Observed a significant reduction in budding upon Tsg101 targeting via RNA interference.

Conclusions:

  • The arenavirus Z protein functions as the essential counterpart to matrix proteins in other enveloped RNA viruses.
  • The vacuolar protein sorting pathway, particularly Tsg101, plays a critical role in arenavirus budding.
  • These findings provide a foundation for developing novel antiviral strategies against Lassa fever virus and other hemorrhagic fever arenaviruses.

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