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RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is

Simone V Ward1, Cyril X George, Megan J Welch

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.

Proceedings of the National Academy of Sciences of the United States of America
|December 22, 2010
PubMed

Insights

Adenosine deaminase acting on RNA (ADAR1) acts as a restriction factor against measles virus (MV) and other paramyxoviruses. Disruption of ADAR1’s p150 isoform enhances viral replication and cytopathology.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • Measles virus (MV) is a highly infectious human pathogen causing severe disease, including subacute sclerosing panencephalitis (SSPE).
  • A-to-G hypermutations in the MV genome suggest a role for adenosine deaminase acting on RNA (ADAR1).

Purpose of the Study:

  • To investigate the role of the interferon-inducible p150 isoform of ADAR1 in measles virus infection and replication.
  • To determine if ADAR1 functions as a restriction factor against paramyxoviruses and other RNA viruses.

Main Methods:

  • Generated and utilized p150-deficient and wild-type mouse embryo fibroblast (MEF) cells expressing the MV receptor SLAM.
  • Infected MEF cells with MV and other viruses, assessing syncytium formation, cytopathic effect (CPE), and viral titers.
  • Disrupted ADAR1 expression to evaluate its impact on viral replication.

Main Results:

  • p150-deficient MEF cells exhibited significant syncytium formation and cytopathic effect upon MV infection, unlike wild-type cells.
  • MV titers were significantly higher (3-4 log) in p150-deficient cells compared to wild-type cells.
  • ADAR1 disruption did not affect vesicular stomatitis virus, reovirus, or lymphocytic choriomeningitis virus replication but protected against Newcastle disease virus, Sendai virus, canine distemper virus, and influenza A virus.

Conclusions:

  • The p150 isoform of ADAR1 acts as a restriction factor against measles virus replication.
  • ADAR1 plays a crucial role in restricting the replication of certain paramyxoviruses and orthomyxoviruses.

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