Abstract
Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea-induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3263-3277 |
| Number of pages | 15 |
| Journal | Journal of Experimental Medicine |
| Volume | 214 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2017 |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections. / Sun, Lei; Jiang, Zhengfan; Acosta-Rodriguez, Victoria A.; Berger, Michael; Du, Xin; Choi, Jin Huk; Wang, Jianhui; Wang, Kuan wen; Kilaru, Gokhul K.; Mohawk, Jennifer A.; Quan, Jiexia; Scott, Lindsay; Hildebrand, Sara; Li, Xiaohong; Tang, Miao; Zhan, Xiaoming; Murray, Anne R.; Vine, Diantha La; Moresco, Eva Marie Y.; Takahashi, Joseph S.; Beutler, Bruce.
In: Journal of Experimental Medicine, Vol. 214, No. 11, 01.11.2017, p. 3263-3277.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HCFC2 is needed for IRF1- and IRF2-dependent Tlr3 transcription and for survival during viral infections
AU - Sun, Lei
AU - Jiang, Zhengfan
AU - Acosta-Rodriguez, Victoria A.
AU - Berger, Michael
AU - Du, Xin
AU - Choi, Jin Huk
AU - Wang, Jianhui
AU - Wang, Kuan wen
AU - Kilaru, Gokhul K.
AU - Mohawk, Jennifer A.
AU - Quan, Jiexia
AU - Scott, Lindsay
AU - Hildebrand, Sara
AU - Li, Xiaohong
AU - Tang, Miao
AU - Zhan, Xiaoming
AU - Murray, Anne R.
AU - Vine, Diantha La
AU - Moresco, Eva Marie Y.
AU - Takahashi, Joseph S.
AU - Beutler, Bruce
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea-induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.
AB - Transcriptional regulation of numerous interferon-regulated genes, including Toll-like receptor 3 (Tlr3), which encodes an innate immune sensor of viral double-stranded RNA, depends on the interferon regulatory factor 1 (IRF1) and IRF2 transcription factors. We detected specific abrogation of macrophage responses to polyinosinic-polycytidylic acid (poly(I:C)) resulting from three independent N-ethyl-N-nitrosourea-induced mutations in host cell factor C2 (Hcfc2). Hcfc2 mutations compromised survival during influenza virus and herpes simplex virus 1 infections. HCFC2 promoted the binding of IRF1 and IRF2 to the Tlr3 promoter, without which inflammatory cytokine and type I IFN responses to the double-stranded RNA analogue poly(I:C) are reduced in mouse macrophages. HCFC2 was also necessary for the transcription of a large subset of other IRF2-dependent interferon-regulated genes. Deleterious mutations of Hcfc2 may therefore increase susceptibility to diverse infectious diseases.
UR - http://www.scopus.com/inward/record.url?scp=85033392643&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85033392643&partnerID=8YFLogxK
U2 - 10.1084/jem.20161630
DO - 10.1084/jem.20161630
M3 - Article
C2 - 28970238
AN - SCOPUS:85033392643
VL - 214
SP - 3263
EP - 3277
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 11
ER -