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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

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Novel modulators of p53-signaling encoded by unknown genes of emerging viruses

Dina Alzhanova1,2, Kathleen Corcoran1,2, Aubrey G Bailey1,2

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.

Plos Pathogens
|January 7, 2021
PubMed

Insights

Researchers explored unknown viral proteins to find new ways viruses interact with the p53 protein, crucial for cancer and immunity. They identified two viral proteins that bind to p53, showing all viruses interfere with this key cellular defense.

Area of Science:

  • Virology
  • Molecular Biology
  • Cancer Research

Background:

  • The p53 transcription factor is vital in cellular responses to DNA damage, cancer development, and viral infections.
  • The ORFEOME project aimed to uncover novel p53-virus interactions within uncharacterized viral open reading frames (orfs).

Purpose of the Study:

  • To identify and characterize novel interactions between the p53 protein and proteins encoded by unknown viral orfs.
  • To investigate the functional significance of these interactions in the context of viral infection and host defense.

Main Methods:

  • Synthesized and validated 172 orfs of unknown function from diverse emerging viruses, including SARS-Coronavirus, MERS-Coronavirus, influenza, Ebola, Zika (ZIKV), Chikungunya, and Kaposi Sarcoma-associated herpesvirus (KSHV).
  • Performed a functional screen to assess the impact of these viral orfs on p53 signaling pathways.

Main Results:

  • Discovered novel mechanisms by which viruses interact with the p53 pathway.
  • Identified two specific viral proteins, KSHV orf10 and ZIKV NS2A, that directly bind to the p53 protein.
  • Confirmed that viral interference with p53 function extends to both RNA and DNA viruses.

Conclusions:

  • These findings expand our understanding of virus-host interactions, particularly concerning the p53 tumor suppressor.
  • The study validates the ORFEOME resource for systems biology approaches to discover functions of uncharacterized viral elements like proteins, long non-coding RNAs, and microRNAs.
  • Reinforces the conserved strategy of viruses to manipulate the p53 pathway for their replication and survival.

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