Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems

Simon B. Rasmussen, Louise N. Sørensen, Lene Malmgaard, Nina Ank, Joel D. Baines, Zhijian J. Chen, Søren R. Paludan

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-α/β) response is derived from several cell types and induced independently of TLR9. In conventional DCs, the IFN response occurred independently of viral replication but was dependent on viral entry. Moreover, using a HSV-1 UL15 mutant, which fails to package viral DNA into the virion, we found that entry-dependent IFN induction also required the presence of viral genomic DNA. In macrophages and fibroblasts, where the virus was able to replicate, HSV-induced IFN-α/β production was dependent on both viral entry and replication, and ablated in cells unable to signal through the mitochondrial antiviral signaling protein pathway. Thus, during an HSV infection in vivo, multiple mechanisms of pathogen recognition are active, which operate in cell-type- and time-dependent manners to trigger expression of type I IFN and coordinate the antiviral response.

Original languageEnglish (US)
Pages (from-to)13315-13324
Number of pages10
JournalJournal of Virology
Volume81
Issue number24
DOIs
StatePublished - Dec 2007

Fingerprint

Toll-Like Receptor 9
herpes simplex
Interferon Type I
Virus Diseases
interferons
Simplexvirus
Interferons
Antiviral Agents
viruses
infection
Viral DNA
Proteins
proteins
cells
Viruses
Pattern Recognition Receptors
Interferon-beta
Human Herpesvirus 1
Interferon-alpha
Germ Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems. / Rasmussen, Simon B.; Sørensen, Louise N.; Malmgaard, Lene; Ank, Nina; Baines, Joel D.; Chen, Zhijian J.; Paludan, Søren R.

In: Journal of Virology, Vol. 81, No. 24, 12.2007, p. 13315-13324.

Research output: Contribution to journalArticle

@article{15c993fe79504f31aa95995fd9ce3f6c,
title = "Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems",
abstract = "Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-α/β) response is derived from several cell types and induced independently of TLR9. In conventional DCs, the IFN response occurred independently of viral replication but was dependent on viral entry. Moreover, using a HSV-1 UL15 mutant, which fails to package viral DNA into the virion, we found that entry-dependent IFN induction also required the presence of viral genomic DNA. In macrophages and fibroblasts, where the virus was able to replicate, HSV-induced IFN-α/β production was dependent on both viral entry and replication, and ablated in cells unable to signal through the mitochondrial antiviral signaling protein pathway. Thus, during an HSV infection in vivo, multiple mechanisms of pathogen recognition are active, which operate in cell-type- and time-dependent manners to trigger expression of type I IFN and coordinate the antiviral response.",
author = "Rasmussen, {Simon B.} and S{\o}rensen, {Louise N.} and Lene Malmgaard and Nina Ank and Baines, {Joel D.} and Chen, {Zhijian J.} and Paludan, {S{\o}ren R.}",
year = "2007",
month = "12",
doi = "10.1128/JVI.01167-07",
language = "English (US)",
volume = "81",
pages = "13315--13324",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "24",

}

TY - JOUR

T1 - Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems

AU - Rasmussen, Simon B.

AU - Sørensen, Louise N.

AU - Malmgaard, Lene

AU - Ank, Nina

AU - Baines, Joel D.

AU - Chen, Zhijian J.

AU - Paludan, Søren R.

PY - 2007/12

Y1 - 2007/12

N2 - Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-α/β) response is derived from several cell types and induced independently of TLR9. In conventional DCs, the IFN response occurred independently of viral replication but was dependent on viral entry. Moreover, using a HSV-1 UL15 mutant, which fails to package viral DNA into the virion, we found that entry-dependent IFN induction also required the presence of viral genomic DNA. In macrophages and fibroblasts, where the virus was able to replicate, HSV-induced IFN-α/β production was dependent on both viral entry and replication, and ablated in cells unable to signal through the mitochondrial antiviral signaling protein pathway. Thus, during an HSV infection in vivo, multiple mechanisms of pathogen recognition are active, which operate in cell-type- and time-dependent manners to trigger expression of type I IFN and coordinate the antiviral response.

AB - Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-α/β) response is derived from several cell types and induced independently of TLR9. In conventional DCs, the IFN response occurred independently of viral replication but was dependent on viral entry. Moreover, using a HSV-1 UL15 mutant, which fails to package viral DNA into the virion, we found that entry-dependent IFN induction also required the presence of viral genomic DNA. In macrophages and fibroblasts, where the virus was able to replicate, HSV-induced IFN-α/β production was dependent on both viral entry and replication, and ablated in cells unable to signal through the mitochondrial antiviral signaling protein pathway. Thus, during an HSV infection in vivo, multiple mechanisms of pathogen recognition are active, which operate in cell-type- and time-dependent manners to trigger expression of type I IFN and coordinate the antiviral response.

UR - http://www.scopus.com/inward/record.url?scp=37049010982&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=37049010982&partnerID=8YFLogxK

U2 - 10.1128/JVI.01167-07

DO - 10.1128/JVI.01167-07

M3 - Article

VL - 81

SP - 13315

EP - 13324

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 24

ER -