Induction of innate immune responses by SIV in vivo and in vitro: Differential expression and function of RIG-I and MDA5

Research output: Contribution to journalArticle

Abstract

Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.

Original languageEnglish (US)
Pages (from-to)1104-1114
Number of pages11
JournalJournal of Infectious Diseases
Volume204
Issue number7
DOIs
StatePublished - Oct 1 2011

Fingerprint

Simian Immunodeficiency Virus
Tretinoin
Innate Immunity
Virus Diseases
Genes
Macaca
Interferons
Brain
Interferon Type I
Messenger RNA
Double-Stranded RNA
Small Interfering RNA
Proteins
Macrophages
IFIH1 Interferon-Induced Helicase
In Vitro Techniques
RNA
Ligands

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

@article{64e5f5fb8c6242db992deb4180045449,
title = "Induction of innate immune responses by SIV in vivo and in vitro: Differential expression and function of RIG-I and MDA5",
abstract = "Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.",
author = "Co, {Juliene G.} and Witwer, {Kenneth Whitaker} and Lucio Gama and Zink, {Mary Christine} and Clements, {Janice E}",
year = "2011",
month = "10",
day = "1",
doi = "10.1093/infdis/jir469",
language = "English (US)",
volume = "204",
pages = "1104--1114",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "7",

}

TY - JOUR

T1 - Induction of innate immune responses by SIV in vivo and in vitro

T2 - Differential expression and function of RIG-I and MDA5

AU - Co, Juliene G.

AU - Witwer, Kenneth Whitaker

AU - Gama, Lucio

AU - Zink, Mary Christine

AU - Clements, Janice E

PY - 2011/10/1

Y1 - 2011/10/1

N2 - Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.

AB - Interferon-β induction occurs during acute simian immunodeficiency virus (SIV) infection in the brain. We have examined expression and function of cytosolic RNA sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation-associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and protein were expressed at higher levels in the brain than RIG-I, with protein expression correlating with the severity of disease from 42 until 84 days post-inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV infection leads to the production of double-stranded RNA in vivo, which may act as the MDA5 ligand. We have shown for the first time to our knowledge the functional role of MDA5 in the innate immune response to SIV infection.

UR - http://www.scopus.com/inward/record.url?scp=80052518621&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052518621&partnerID=8YFLogxK

U2 - 10.1093/infdis/jir469

DO - 10.1093/infdis/jir469

M3 - Article

C2 - 21881126

AN - SCOPUS:80052518621

VL - 204

SP - 1104

EP - 1114

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 7

ER -