Kui Li, PhD

Our research is aimed at understanding virus-host interactions that regulate pathogenesis and outcome of RNA virus infections. Currently, work in the Li laboratory is centered on two main themes. The first one is to dissect innate immunity to infections by positive-strand RNA viruses such as hepatitis C virus and related viruses. We are studying how these viruses are detected by host innate immune sensors such as the Toll-like receptors and RIG-I-like receptors, leading to antiviral and inflammatory responses. The second focus area is to investigate how TRIM56, a tripartite motif protein, contributes to innate antiviral immunity. Studies are ongoing to delineate the molecular determinants by which TRIM56 restricts RNA virus infections and by which it promotes innate immune signaling. To study these themes, we employ virus-cell culture systems and various biochemical, cell biological and molecular approaches.

• Chen Z, Benureau Y, Rijnbrand R, Yi JZ, Wang T, Walters L, Lanford RE, Weinman SA, Lemon SM, Martin A, and Li K. GB virus B disrupts RIG-I signaling by NS3/4A-mediated cleavage of the adaptor protein MAVS. Journal of Virology 2007; 81: 964-976.
• Chen Z, Rijnbrand R, Jangra R, Devaraj SG, Qu L, Ma YH, Lemon SM, and Li K. Ubiquitination and proteasomal degradation of interferon regulatory factor-3 induced by Npro from a cytopathic bovine viral diarrhea virus. Virology 2007; 366: 277-292. 
• Devaraj SG, Wang N, Chen ZB, Chen Z, Tseng M, Barretto N, Lin R, Peters CJ, Tseng CT, Baker SC, and Li K. Regulation of IRF-3-dependent innate immunity by the papain-like protease domain of the severe acute respiratory syndrome coronavirus. Journal of Biological Chemistry 2007; 282:32208-32221. 
• Wang N, Liang Y, Devaraj SG, Wang J, Lemon SM, and Li K. Toll-like receptor 3 mediates establishment of an antiviral state against hepatitis C virus in hepatoma cells. Journal of Virology 2009; 83: 9824-9834.
• Wang N, Dong Q, Li J, Jangra RK, Fan M, Brasier AR, Lemon SM, Pfeffer LM, and Li K. Viral induction of the zinc-finger antiviral protein is IRF3-dependent but NF-kB-independent. Journal of Biological Chemistry 2010; 285: 6080-6090. 
• Song HS, Li J, Shi S, Yan L, Zhuang H, and Li K. Thermal stability and inactivation of hepatitis C virus grown in cell culture. Virology Journal 2010; 7: 40.
• Zhou Z, Wang N, Woodson SE, Dong Q, Wang J, Liang Y, Rijnbrand R, Wei L, Nichols JE, Guo JT, Holbrook MR, Lemon SM, and Li K. Antiviral activities of ISG20 in positive-strand RNA virus infections. Virology 2011; 409:175-188.
• Wang J, Liu B, Wang N, Lee YM, Liu C, and Li K. TRIM56 is a virus- and interferon-inducible E3 ubiquitin ligase that restricts pestivirus infection. Journal of Virology 2011; 85:3733-3745.
• Li NL, Dong Q, Wei D, Pfeffer SR, Fan M, Pfeffer LM, and Li K. Activation of chemokine and inflammatory cytokine response in hepatitis C virus-infected hepatocytes depends on Toll-like receptor 3 sensing of hepatitis C virus double-stranded RNA intermediates. Hepatology 2012; 55:666-675.
• Song H, Ren F, Li J, Shi S, Yan L, Gao F, Li K, and Zhuang H. A laboratory-adapted HCV JFH-1 strain is sensitive to neutralization and can gradually escape under the selection pressure of neutralizing human plasma. Virus Research 2012; 169: 154-161.
• Shen Y, Li NL, Wang J, Liu B, Lester S, and Li K. TRIM56 is an essential component of the TLR3 antiviral signaling pathway. Journal of Biological Chemistry 2012; 287:36404-36413.
• Li K and Lemon SM. Innate immune responses in hepatitis C virus infection. Seminars in Immunopathology 2013; 35:53-72.
• Lester SN and Li K. Toll-like receptors in antiviral innate immunity. Journal of Molecular Biology 2014; 426:1246-1264
• Liu B, Li NL, Wang J, Wang T, Miller MA, and Li K. Overlapping and distinct molecular determinants dictating the antiviral activities of TRIM56 against flaviviruses and coronavirus. Journal of Virology 2014; 88:13821-13835.
• Liu B, Li NL, Shen Y, Bao X, Fabrizio T, Elbahesh H, Webby RJ, and Li K. The C-terminal tail of TRIM56 dictates antiviral restriction of influenza A and B viruses by impeding viral RNA synthesis. Journal of Virology 2016; 90:4369-4382.
• Wei D, Li NL, Zeng Y, Liu B, Kumthip K, Wang TT, Huo D, Ingels JF, Lu L, Shang J, and Li K. The molecular chaperone GRP78 contributes to Toll-like receptor-3-mediated innate immune response to hepatitis C virus in hepatocytes. Journal of Biological Chemistry 2016; 291:12294-12309.
• Kumthip K, Yang D, Li NL, Zhang Y, Fan M, Sethuraman A, and Li K. Pivotal role for the ESCRT-II complex subunit EAP30/SNF8 in IRF3-dependent innate antiviral defense. PLoS Pathogens 2017; 13(10): e1006713.
• Yang D, Li NL, Wei D, Liu B, Guo F, Elbahesh H, Zhang Y, Zhou Z, Chen GY, and Li K. The E3 ligase TRIM56 is a host restriction factor of Zika virus and depends on its RNA-binding activity but not miRNA regulation, for antiviral function. PLoS Neglected Tropical Diseases 2019; 13(6): e0007537.
• Li K, Shen Y, Miller MA, Stabenow J, Williams RW, and Lu L. Differing susceptibility of C57BL/6J and DBA/2J mice — parents of the murine BXD family, to severe acute respiratory syndrome coronavirus infection. Cell & Bioscience 2021; 11:137.
• Wang D, Wang R, and Li K. Impaired antiviral responses to extracellular double-stranded RNA and cytosolic DNA, but not to interferon-α stimulation, in TRIM56-deficient cells. Viruses 2022; 14(1):89.

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