Cellular mRNA decay protein AUF1 negatively regulates enterovirus and human rhinovirus infections

Andrea L Cathcart1, Janet M Rozovics, Bert L Semler

  • 1Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, CA 92697 USA.

Journal of Virology
|August 2, 2013
PubMed

Insights

AUF1 protein binds to poliovirus RNA, but viral proteases cleave AUF1, inhibiting this interaction. AUF1 acts as an antiviral factor against picornaviruses like poliovirus, coxsackievirus, and human rhinovirus.

Area of Science:

  • Virology
  • Molecular Biology
  • RNA Biology

Background:

  • Picornaviruses manipulate host proteins for replication.
  • AU-rich binding factor 1 (AUF1) regulates mRNA stability via AU-rich elements (AREs).
  • AUF1 interacts with picornavirus RNA and is cleaved by viral proteases.

Purpose of the Study:

  • To investigate AUF1's interaction with poliovirus 5' NCR and the effect of viral cleavage.
  • To determine AUF1's role in poliovirus replication.
  • To explore AUF1's function against related picornaviruses.

Main Methods:

  • In vitro binding assays to study AUF1 isoform interaction with poliovirus 5' NCR stem-loop IV.
  • Analysis of AUF1 cleavage by viral proteinase 3CD.
  • Immunofluorescence microscopy to observe endogenous AUF1 relocalization in infected cells.
  • Assessment of viral translation and titers in the presence of AUF1.

Main Results:

  • All AUF1 isoforms bind stem-loop IV of the poliovirus 5' NCR.
  • Proteolytic cleavage of AUF1 by viral proteinase 3CD inhibits this binding.
  • Endogenous AUF1 relocalizes to the cytoplasm in infected cells, driven by viral protein 2A.
  • AUF1 inhibits poliovirus translation and reduces viral titers.
  • AUF1 acts as an antiviral factor against coxsackievirus and human rhinovirus.

Conclusions:

  • AUF1 binding to poliovirus RNA is regulated by viral protease-mediated cleavage.
  • AUF1 functions as a host antiviral factor against multiple picornaviruses, including poliovirus, coxsackievirus, and human rhinovirus.
  • Viral manipulation of AUF1 is a common strategy employed by related picornaviruses.

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