Visualization of double-stranded RNA colocalizing with pattern recognition receptors in arenavirus infected cells

Elizabeth J. Mateer, Slobodan Paessler, Cheng Huang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.

Original languageEnglish (US)
Article number251
JournalFrontiers in cellular and infection microbiology
Volume8
Issue numberJUL
DOIs
StatePublished - Jul 24 2018

Fingerprint

Arenavirus
Pattern Recognition Receptors
Double-Stranded RNA
New World Arenaviruses
Viral RNA
Arenaviridae Infections
RNA Viruses
Innate Immunity
Protein Kinases
Exoribonucleases
eIF-2 Kinase
DNA Viruses
Virus Diseases
Interferons

Keywords

  • Arenaviruses
  • DsRNA
  • Junín virus
  • MDA-5
  • Negative-sense RNA virus
  • Pattern recognition receptor
  • PKR
  • RIG-I

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

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title = "Visualization of double-stranded RNA colocalizing with pattern recognition receptors in arenavirus infected cells",
abstract = "An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.",
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author = "Mateer, {Elizabeth J.} and Slobodan Paessler and Cheng Huang",
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AU - Mateer, Elizabeth J.

AU - Paessler, Slobodan

AU - Huang, Cheng

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N2 - An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.

AB - An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.

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