Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection

Bridget A. Robinson, Ryan Estep, Ilhem Messaoudi, Kelsey S. Rogers, Scott Wong

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV 17577 (WT BAC RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT BAC RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT BAC RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.

Original languageEnglish (US)
Pages (from-to)2197-2211
Number of pages15
JournalJournal of Virology
Volume86
Issue number4
DOIs
StatePublished - Feb 2012

Fingerprint

Rhadinovirus
Interferon Type I
Macaca mulatta
interferon-gamma
Interferon-gamma
interferons
Infection
infection
Interferon Regulatory Factor-3
Interferons
mononuclear leukocytes
Blood Cells
Human herpesvirus 8
Interferon Regulatory Factors
Bacterial Artificial Chromosomes
viral interferon regulatory factors
interferon regulatory factors
Human Herpesvirus 8
bacterial artificial chromosomes
dendritic cells

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection. / Robinson, Bridget A.; Estep, Ryan; Messaoudi, Ilhem; Rogers, Kelsey S.; Wong, Scott.

In: Journal of Virology, Vol. 86, No. 4, 02.2012, p. 2197-2211.

Research output: Contribution to journalArticle

Robinson, Bridget A. ; Estep, Ryan ; Messaoudi, Ilhem ; Rogers, Kelsey S. ; Wong, Scott. / Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection. In: Journal of Virology. 2012 ; Vol. 86, No. 4. pp. 2197-2211.
@article{c1283b1c81324080afc17e56f596fd52,
title = "Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection",
abstract = "Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV 17577 (WT BAC RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT BAC RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT BAC RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.",
author = "Robinson, {Bridget A.} and Ryan Estep and Ilhem Messaoudi and Rogers, {Kelsey S.} and Scott Wong",
year = "2012",
month = "2",
doi = "10.1128/JVI.05047-11",
language = "English (US)",
volume = "86",
pages = "2197--2211",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Viral interferon regulatory factors decrease the induction of type I and type II interferon during rhesus macaque rhadinovirus infection

AU - Robinson, Bridget A.

AU - Estep, Ryan

AU - Messaoudi, Ilhem

AU - Rogers, Kelsey S.

AU - Wong, Scott

PY - 2012/2

Y1 - 2012/2

N2 - Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV 17577 (WT BAC RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT BAC RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT BAC RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.

AB - Kaposi's sarcoma-associated herpesvirus and rhesus macaque rhadinovirus (RRV), two closely related gammaherpesviruses, are unique in their expression of viral homologs of cellular interferon regulatory factors (IRFs), termed viral IRFs (vIRFs). To assess the role of vIRFs during de novo infection, we have utilized the bacterial artificial chromosome clone of wild-type RRV 17577 (WT BAC RRV) to generate a recombinant virus with all 8 of the vIRFs deleted (vIRF-ko RRV). The infection of primary rhesus fibroblasts and peripheral blood mononuclear cells (PBMCs) with vIRF-ko RRV resulted in earlier and increased induction of type I interferon (IFN) (IFN-α/β) and type II IFN (IFN-γ). Additionally, plasmacytoid dendritic cells maintained higher levels of IFN-α production in PBMC cultures infected with vIRF-ko RRV than in cultures infected with WT BAC RRV. Moreover, the nuclear accumulation of phosphorylated IRF-3, which is necessary for the induction of type I IFN, was also inhibited following WT BAC RRV infection. These findings demonstrate that during de novo RRV infection, vIRFs are inhibiting the induction of IFN at the transcriptional level, and one potential mechanism for this is the disruption of the activation and localization of IRF-3.

UR - http://www.scopus.com/inward/record.url?scp=84857074309&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857074309&partnerID=8YFLogxK

U2 - 10.1128/JVI.05047-11

DO - 10.1128/JVI.05047-11

M3 - Article

VL - 86

SP - 2197

EP - 2211

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 4

ER -