The Lymphocytic Choriomeningitis Virus Matrix Protein PPXY Late Domain Drives the Production of Defective Interfering Particles

Arenaviruses cause severe diseases in humans but establish asymptomatic, lifelong infections in rodent reservoirs. Persistently-infected rodents harbor high levels of defective interfering (DI) particles, which are thought to be important for establishing persistence and mitigating virus-induced cytopathic effect. Little is known about what drives the production of DI particles. We show that neither the PPXY late domain encoded within the lymphocytic choriomeningitis virus (LCMV) matrix protein nor a functional endosomal sorting complex transport (ESCRT) pathway is absolutely required for the generation of standard infectious virus particles. In contrast, DI particle release critically requires the PPXY late domain and is ESCRT-dependent. Additionally, the terminal tyrosine in the PPXY motif is reversibly phosphorylated and our findings indicate that this posttranslational modification may regulate DI particle formation. Thus we have uncovered a new role for the PPXY late domain and a possible mechanism for its regulation.

• Publication year

  2016

• Venue

  PLoS Pathogens

• Publication date

  2016-03-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.ppat.1005501PMID 27010636PMCID 4806877
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Terminal tyrosine phosphorylation is implicated as a regulator of defective interfering particle formation.

  Confidence 0.86

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• The terminal tyrosine within the PPXY late domain is reversibly phosphorylated.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• Defective interfering particle release critically depends on the PPXY late domain and on ESCRT pathway function.

  Confidence 0.98

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• Standard infectious virus particle production does not absolutely require either the PPXY late domain or a functional ESCRT pathway.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review

• defective interfering particles

  virus particles

  Virus-derived particles with defective genomes that are produced during LCMV infection and are associated with persistent infection.

  Aliases: DI particles

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• escrt pathway

  host pathway

  The host endosomal sorting complex required for transport pathway that mediates membrane scission during virus budding.

  Aliases: ESCRT

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• lcmv matrix protein

  viral protein

  The matrix protein encoded by lymphocytic choriomeningitis virus and examined for its role in particle release.

  Aliases: matrix protein

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• ppxy late domain

  viral motif

  A proline-rich late-domain motif in the LCMV matrix protein that contains the terminal tyrosine residue discussed in the abstract.

  Aliases: PPXY motif

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• standard infectious virus particles

  virus particles

  Fully infectious LCMV particles representing the normal virus output.

  Aliases: infectious virus particles

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review
• terminal tyrosine phosphorylation

  post-translational modification

  Reversible phosphorylation of the terminal tyrosine residue within the PPXY motif of the matrix protein.

  Aliases: phosphorylation of the terminal tyrosine

  박진우 (dztg5apj7m) extractionmexicorea (qjvnbu8xg3) reviewq (76h6bfydm6) review

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