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Viruses go modular

Ariel Shepley-McTaggart1, Hao Fan2,3,4, Marius Sudol5,6,7,8

  • 1Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.

The Journal of Biological Chemistry
|March 1, 2020
PubMed

Insights

Viruses hijack cellular WW domain proteins using the PPxY motif for replication. Understanding these interactions can lead to new antiviral therapies targeting viral PPxY-host WW-domain binding.

Area of Science:

  • Molecular Biology
  • Virology
  • Cellular Biology

Background:

  • WW domains are modular protein structures recognizing the Pro-Pro-x-Tyr (PPxY) motif.
  • These domains mediate protein interactions in cellular signaling pathways like the Hippo pathway.
  • WW domains are crucial in normal cellular functions and disease processes.

Purpose of the Study:

  • To review the mechanisms by which RNA and DNA viruses exploit host WW domain-containing proteins.
  • To highlight the identification of novel virus-host interactions involving WW domains.
  • To explore the potential for developing antiviral therapeutics based on these interactions.

Main Methods:

  • Literature review of existing research on WW domains and viral hijacking.
  • Analysis of identified virus-host interactions and their roles in viral life cycles.
  • Discussion of molecular mechanisms underlying PPxY-WW domain interactions.

Main Results:

  • Viruses utilize WW domains for critical life cycle steps, including entry, replication, and egress.
  • Numerous virus-host interactions involving WW domains have been identified.
  • The PPxY motif is a key element exploited by viruses to interact with host WW domains.

Conclusions:

  • Understanding virus-host WW domain interactions enhances knowledge of viral pathogenesis.
  • These interactions offer potential targets for novel antiviral drug development.
  • Small-molecule inhibitors targeting PPxY-WW domain interactions could serve as new antiviral therapeutics.
Keywords:
E3 ubiquitin ligaseEbola virusL domainPPxY motifWW domainantiviral agentantiviral therapeuticbuddinghost-oriented inhibitorsmicrobiologymodular domainsviral life cyclevirusvirus buddingvirus-host interactionvirus-like particle (VLP)

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