Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity

Sophiya Karki, Melody M H Li, John W. Schoggins, Suyan Tian, Charles M. Rice, Margaret R. MacDonald

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

The zinc finger antiviral protein (ZAP) is a host factor that mediates inhibition of viruses in the Filoviridae, Retroviridae and Togaviridae families. We previously demonstrated that ZAP blocks replication of Sindbis virus (SINV), the prototype Alphavirus in the Togaviridae family at an early step prior to translation of the incoming genome and that synergy between ZAP and one or more interferon stimulated genes (ISGs) resulted in maximal inhibitory activity. The present study aimed to identify those ISGs that synergize with ZAP to mediate Alphavirus inhibition. Using a library of lentiviruses individually expressing more than 350 ISGs, we screened for inhibitory activity in interferon defective cells with or without ZAP overexpression. Confirmatory tests of the 23 ISGs demonstrating the largest infection reduction in combination with ZAP revealed that 16 were synergistic. Confirmatory tests of all potentially synergistic ISGs revealed 15 additional ISGs with a statistically significant synergistic effect in combination with ZAP. These 31 ISGs are candidates for further mechanistic studies. The number and diversity of the identified ZAP-synergistic ISGs lead us to speculate that ZAP may play an important role in priming the cell for optimal ISG function.

Original languageEnglish (US)
Article numbere37398
JournalPLoS One
Volume7
Issue number5
DOIs
StatePublished - May 16 2012

Fingerprint

antiviral proteins
Alphavirus
zinc finger motif
Zinc Fingers
interferons
Interferons
Antiviral Agents
Zinc
Genes
Proteins
genes
Togaviridae
Viruses
Filoviridae
Retroviridae
Sindbis virus
Sindbis Virus
Lentivirus
prototypes
translation (genetics)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. / Karki, Sophiya; Li, Melody M H; Schoggins, John W.; Tian, Suyan; Rice, Charles M.; MacDonald, Margaret R.

In: PLoS One, Vol. 7, No. 5, e37398, 16.05.2012.

Research output: Contribution to journalArticle

Karki, Sophiya ; Li, Melody M H ; Schoggins, John W. ; Tian, Suyan ; Rice, Charles M. ; MacDonald, Margaret R. / Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. In: PLoS One. 2012 ; Vol. 7, No. 5.
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