Chapter 11 : Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity

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Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, Page 1 of 2

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This chapter explores three categories in which antiviral signaling, either activated by virus or active within a noninfectious context, can significantly modulate pathology. After briefly reviewing antiviral signaling, the chapter summarizes recent findings that investigate the connection between the host antiviral and antibacterial responses. It explains long-known clinical observations that viral infections can affect a patient’s susceptibility to bacteria. The chapter discusses how antiviral signaling can modulate the adaptive immune system and thereby result in enhanced or reduced, autoimmunity and inflammation. It also explores the profound metabolic consequences of the host response to viral infection and specifically elaborates how such signaling can cross talk with nuclear receptor (NR) pathways critical for metabolism of lipids and xenobiotics, leading to atherosclerosis and hepatic pathology, respectively. The interaction of the immune complexes with toll-like receptors 9 (TLR9) has been shown to promote systemic autoimmune diseases such as systemic lupus erythematosus (SLE). The chapter focuses on the role of type I interferon (IFN) in promoting and inhibiting autoimmunity. Results from one study suggested the possibility of IFN-mediated immune therapy for glomerulonephritis. It has long been known that several pathogens known as the toxoplasma, rubella, cytomegalovirus, and herpes simplex virus (TORCH) organisms can cause severe developmental defects during gestation. Importantly, in the cases of autoimmune disease it appears that the IFN system can affect the development and progress of pathology in the absence of any viral infection.

Citation: Razani B, Shahangian A, Cheng G, Guo B. 2009. Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, p 155-175. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch11

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Immune Systems
Systemic Lupus Erythematosus
Major Histocompatibility Complex
Tumor Necrosis Factor
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Figure 1

(A) Contribution of TLR and IFN pathways to the pathogenesis of the systemic autoimmune disease SLE. (B) Role of type I IFN induction pathway in the anti-inflammatory response and in suppression of Th17-mediated, tissue-specific autoimmune diseases. (C) Cross talk between type I IFN and TGF-β in regulating mesangial cell proliferation and glomerulonephritis. IBD, inflammatory bowel disease.

Citation: Razani B, Shahangian A, Cheng G, Guo B. 2009. Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, p 155-175. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch11
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Figure 2

Antiviral signaling initiated by intracellular PRRs or TLR3 activation leads to an IRF3-mediated inhibition of LXR- and RXR-dependent gene transcription. Important targets of these NRs include cholesterol exporters in macrophages and aspirin-metabolizing enzymes in hepatocytes, respectively, which can enhance atherosclerosis or the aspirin-associated postviral hepatitis characteristic of Reye’s syndrome. dsRNA, double-stranded RNA.

Citation: Razani B, Shahangian A, Cheng G, Guo B. 2009. Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, p 155-175. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch11
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Figure 3

Outcomes of antiviral signaling initiated by PRRs or IFNAR affect host physiology in multiple ways in addition to defense against viral infection. These include modulation of antibacterial defense, adaptive immunity, and metabolic signaling.

Citation: Razani B, Shahangian A, Cheng G, Guo B. 2009. Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, p 155-175. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch11
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Table 1

Effects of type I interferons on host response to bacterial infection

Citation: Razani B, Shahangian A, Cheng G, Guo B. 2009. Biological Impact of Type I Interferon Induction Pathways beyond Their Antivirus Activity, p 155-175. In Brasier A, García-Sastre A, Lemon S (ed), Cellular Signaling and Innate Immune Responses to RNA Virus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555815561.ch11

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