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

24 Citations (Scopus)

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

Fingerprint

interferon-alpha
Orthomyxoviridae
Virus Replication
virus replication
Interferon-alpha
Primates
interferons
Interferons
gene expression
Genes
Vero Cells
RNA
cells
Messenger RNA
Influenza A virus
genomics
transcription (genetics)
Genome
Pattern Recognition Receptors
human influenza

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells. / Matzinger, Shannon R.; Carroll, Timothy D.; Dutra, Joseph C.; Ma, Zhong Min; Miller, Chris J.

In: Journal of Virology, Vol. 87, No. 2, 01.2013, p. 1150-1158.

Research output: Contribution to journalArticle

Matzinger, Shannon R. ; Carroll, Timothy D. ; Dutra, Joseph C. ; Ma, Zhong Min ; Miller, Chris J. / Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells. In: Journal of Virology. 2013 ; Vol. 87, No. 2. pp. 1150-1158.
@article{62438aa86e6e4eef9386219a0bb5cb7f,
title = "Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells",
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.",
author = "Matzinger, {Shannon R.} and Carroll, {Timothy D.} and Dutra, {Joseph C.} and Ma, {Zhong Min} and Miller, {Chris J}",
year = "2013",
month = "1",
doi = "10.1128/JVI.02271-12",
language = "English (US)",
volume = "87",
pages = "1150--1158",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "2",

}

TY - JOUR

T1 - Myxovirus resistance gene a (MXA) expression suppresses influenza a virus replication in alpha interferon-treated primate cells

AU - Matzinger, Shannon R.

AU - Carroll, Timothy D.

AU - Dutra, Joseph C.

AU - Ma, Zhong Min

AU - Miller, Chris J

PY - 2013/1

Y1 - 2013/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84871949114&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871949114&partnerID=8YFLogxK

U2 - 10.1128/JVI.02271-12

DO - 10.1128/JVI.02271-12

M3 - Article

C2 - 23152507

AN - SCOPUS:84871949114

VL - 87

SP - 1150

EP - 1158

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 2

ER -