West Nile virus (WNV) is an emerging infectious disease of public health importance. In humans, WNV can cause a life threatening illness and damage to the central nervous system (CNS). We have linked WNV infection outcome with the regulation of host cell pathogen recognition receptor (PRR) signaling programs of innate immunity that trigger interferon alpha/beta expression and that activate interferon regulatory factors (IRFs) to induce antiviral response genes that control infection. We now propose to determine the specific PRRs, IRFs, and their intracellular signaling pathways that control cell-specific imimune defenses and the outcome of WNV infection. Our studies will 1) Determine the effect of specific PRR and IRF genes on cell tropism of WNV infection, and 2) Define the PRRs and IRFs that serve to control CNS entry and pathogenesis of WNV infection. These studies will reveal the host innate immune signaling and response features that control WNV infection.
West Nile virus (WNV) is an emerging virus that causes central nervous system damage that can disable and kill infected people and other animals. Our studies have linked WNV pathogenesis with viral control of the host cell innate immune response to infection. These studies indicate that the control of innate immuity is essential for controlling WNV infection and disease. This project is therefore focused on understanding the virus-host itneractions of WNV infection that regulate innate immunity and overall infection outcome. Our primary goal is to identify specific virus-host interactions that regulate innate immune defenses in specific cell types, incouding the central nervous system, with a larger goal of exploiting these interactions in therapeutic strategies to enhance immunity and limit WNV infection and disease.
| Luo, Huanle; Winkelmann, Evandro; Xie, Guorui et al. (2017) MAVS Is Essential for Primary CD4+ T Cell Immunity but Not for Recall T Cell Responses following an Attenuated West Nile Virus Infection. J Virol 91: |
| Quicke, Kendra M; Diamond, Michael S; Suthar, Mehul S (2017) Negative regulators of the RIG-I-like receptor signaling pathway. Eur J Immunol 47:615-628 |
| Zhao, Jincun; Vijay, Rahul; Zhao, Jingxian et al. (2016) MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis. J Virol 90:7098-7108 |
| Nair, Sharmila; Diamond, Michael S (2015) Innate immune interactions within the central nervous system modulate pathogenesis of viral infections. Curr Opin Immunol 36:47-53 |
| Lazear, Helen M; Nice, Timothy J; Diamond, Michael S (2015) Interferon-?: Immune Functions at Barrier Surfaces and Beyond. Immunity 43:15-28 |
| Lazear, Helen M; Daniels, Brian P; Pinto, Amelia K et al. (2015) Interferon-? restricts West Nile virus neuroinvasion by tightening the blood-brain barrier. Sci Transl Med 7:284ra59 |
| Kell, Alison M; Gale Jr, Michael (2015) RIG-I in RNA virus recognition. Virology 479-480:110-21 |
| Chakrabarti, Arindam; Banerjee, Shuvojit; Franchi, Luigi et al. (2015) RNase L activates the NLRP3 inflammasome during viral infections. Cell Host Microbe 17:466-77 |
| Hussmann, Katherine L; Vandergaast, Rianna; Ochsner, Susan Park et al. (2014) In vitro and in vivo characterization of a West Nile virus MAD78 infectious clone. Arch Virol 159:3113-8 |
| Zhao, Jincun; Li, Kun; Wohlford-Lenane, Christine et al. (2014) Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A 111:4970-5 |
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