Roles of the three L-domains in β-retrovirus budding

Chisato Narahara1,2, Jiro Yasuda1,2

  • 1Department of Emerging Infectious Diseases, Institute of Tropical Medicine (NEKKEN).

Insights

The PPxY motif is crucial for Mason-Pfizer monkey virus (M-PMV) replication, acting as a major L-domain across cell types. The PSAP motif

Area of Science:

  • * Virology
  • * Molecular Biology
  • * Cell Biology

Background:

  • * Retroviral Gag protein is essential for virus budding.
  • * L-domains (PT/SAP, PPxY, YxxL, FPIV) within Gag regulate efficient budding.
  • * Mason-Pfizer monkey virus (M-PMV) Gag contains PSAP, PPxY, and YADL motifs.

Purpose of the Study:

  • * To investigate the roles of M-PMV Gag's PSAP, PPxY, and YADL sequences in virus replication.
  • * To determine the cell-type dependency of these motifs in M-PMV budding.
  • * To elucidate the function of the YADL motif in M-PMV production.

Main Methods:

  • * Mutational analysis of M-PMV Gag sequences (PSAP, PPxY, YADL).
  • * Assessment of virus replication and progeny production in 293T, COS-7, and HeLa cells.
  • * Evaluation of Gag protein transport to the plasma membrane.

Main Results:

  • * The PPxY motif is a critical L-domain for M-PMV progeny virus production in all tested cell lines.
  • * The PSAP motif functions as an additional L-domain in HeLa cells but is dispensable in 293T and COS-7 cells.
  • * The YADL motif is required for Gag transport to the plasma membrane, not as an L-domain.

Conclusions:

  • * M-PMV utilizes multiple L-domains, with PPxY being essential and PSAP showing cell-type-dependent function.
  • * Viruses adapt L-domain usage for replication across different cellular environments.
  • * The YADL motif acts as a Gag transport signal, distinct from its role in viral budding.

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