Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells

Shannon R. Matzinger, Timothy D. Carroll, Joseph C. Dutra, Zhong Min Ma, Chris J Miller

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Alpha interferon (IFN-α) production is triggered when influenza virus RNA is detected by appropriate pattern recognition receptors in the host cell. IFN-α induces the expression of more than 300 interferon-stimulated genes (ISGs), and this blunts influenza virus replication. The human ISG MxA can inhibit influenza A virus replication in mouse cells by interfering with a step in the virus replication cycle after primary transcription of the negative-strand RNA genome to mRNA (J. Pavlovic, O. Haller, and P. Staeheli, J. Virol. 66:2564-2569, 1992). To determine the role of MxA in blocking human influenza A virus replication in primate cells, we manipulated MxA expression in rhesus kidney epithelial cells (LLC-MK2) and human lung carcinoma cells (A549). We found that IFN-α treatment prior to influenza virus infection suppressed virus replication and induced the expression of many ISGs, including MxA. However, IFN-α-mediated suppression of virus replication was abolished by small interfering RNA (siRNA) knockdown of MxA expression in IFN-treated cells. In addition, influenza virus replication was suppressed in Vero cells stably transfected with MxA. A strand-specific reverse transcription-PCR (RT-PCR) assay showed that positive-strand influenza virus mRNA and negative-strand genomic RNA (gRNA) accumulated to high levels at 8 h after infection in control Vero cells containing the empty vector. However, in Vero cells stably transfected with MxA positive-strand influenza virus mRNA, complementary positive-strand influenza virus genome RNA (cRNA) and influenza virus gRNA were drastically suppressed. Thus, in primate cells, MxA inhibits human seasonal influenza virus replication at a step prior to primary transcription of gRNA into mRNA. Taken together, these results demonstrate that MxA mediates control of influenza virus replication in primate cells treated with IFN-α.

Original languageEnglish (US)
Pages (from-to)1150-1158
Number of pages9
JournalJournal of Virology
Volume87
Issue number2
DOIs
StatePublished - Jan 2013

ASJC Scopus subject areas

  • Immunology
  • Virology

Fingerprint Dive into the research topics of 'Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells'. Together they form a unique fingerprint.

  • Cite this