Melody Man Hing Li , PH.D.
Assistant Professor, Microbiology, Immunology & Molecular Genetics,
Member, AIDS Institute
Member, Broad Stem Cell Research Center
Member, Inflammation, Immunity, Infection, & Transplantation Theme (I3T)
Member, Molecular Biology Institute
Member, Immunity, Microbes & Molecular Pathogenesis GPB Home Area, Genetics & Genomics GPB Home Area
Mosquito-borne viruses are emerging pathogens that cause devastating outbreaks worldwide as globalization and climate change facilitate their spread beyond their endemic regions. The Li laboratory studies the host type I interferon (IFN) response to medically relevant mosquito-borne viruses such as alphaviruses and flaviviruses. Cellular sensing of viral pathogens triggers IFN production and signaling leading to expression of a wide array of IFN-stimulated genes (ISGs) with antiviral activities. In particular, zinc finger antiviral protein (ZAP) targets diverse viruses by recognition of CG dinucleotide, recruitment of cellular RNA decay machineries, and suppression of viral translation. However, what determines the broad yet specific activity of ZAP is poorly understood. We discovered that ZAP co-opts the host ubiquitination pathway to block viral translation, and some alphaviruses have evolved strategies to evade ZAP antiviral action. Understanding how cellular and viral processes modulate ISG antiviral function will shed light on the molecular mechanisms driving viral virulence and pathogenesis. In addition, recent studies by other groups have pointed to an unexpected role of IFNs; both type I and type III IFNs can decrease blood-brain barrier permeability in a mouse viral infection model. We are interested in the pro-barrier functions of IFNs as our previous work suggested that IRF2, a negative regulator of IFN, protects the central nervous system from alphaviral invasion and encephalitis. A full characterization of ISG activities will elucidate the basic biology of host pathogen recognition and uncover cellular processes required for the success or suppression of viral replication, which will inform the development of broad-spectrum antiviral therapeutic.
Dr. Li is an Assistant Professor of Microbiology, Immunology and Molecular Genetics at UCLA. She received her Bachelors of Science Degree (B.S.) from University of California, Irvine in 2006, and her Doctor of Philosophy Degree (Ph.D.) in Microbiology from University of Washington, Seattle in 2011. Dr. Li’s thesis work elucidated the functional consequences of polymorphisms in the human APOBEC3H gene, which encodes for a cytosine deaminase that is antiviral against human immunodeficiency virus type 1 (HIV-1). Dr. Li subsequently completed her postdoctoral work at Rockefeller University where she studied the antiviral mechanisms and regulation of the host interferon response targeting alphaviruses. Dr. Li established her own laboratory at UCLA in 2017, and her research focuses on elucidating the role of ISGs in innate immunity and blood-brain barrier integrity with broad implications for the treatment of viral infections, autoimmunity and neurological diseases. She serves on the UCLA Basic/Translational COVID-19 Research Committee.
Garcia G Jr, Paul S, Beshara S, Ramanujan VK, Ramaiah A, Nielsen-Saines K, Li MMH, French SW, Morizono K, Kumar A, Arumugaswami V. Hippo Signaling Pathway Has a Critical Role in Zika Virus Replication and in the Pathogenesis of Neuroinflammation. Am J Pathol. 2020 Apr;190(4):844-861. doi: 10.1016/j.ajpath.2019.12.005. Epub 2020 Feb 5. PMID: 32035058; PMCID: PMC7163250.
Li MMH, Aguilar EG, Michailidis E, Pabon J, Park P, Wu X, de Jong YP, Schneider WM, Molina H, Rice CM, MacDonald MR. Characterization of Novel Splice Variants of Zinc Finger Antiviral Protein (ZAP). J Virol. 2019 Aug 28;93(18):e00715-19. doi: 10.1128/JVI.00715-19. PMID: 31118263; PMCID: PMC6714797.
Law LMJ, Razooky BS, Li MMH, You S, Jurado A, Rice CM, MacDonald MR. ZAP’s stress granule localization is correlated with its antiviral activity and induced by virus replication. PLoS Pathog. 2019 May 22;15(5):e1007798. doi: 10.1371/journal.ppat.1007798. PMID: 31116799; PMCID: PMC6548403.
Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann HH, Wang Y, Silva LAV, Sarbanes S, Sun T, Andrus L, Yu Y, Quirk C, Li M, MacDonald MR, Schneider WM, An X, Rosenberg BR, Rice CM. Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell. 2018 Jan 25;172(3):423-438.e25. doi: 10.1016/j.cell.2017.11.018. Epub 2017 Dec 14. PMID: 29249360; PMCID: PMC5786493.
Li Melody M H, Lau Zerlina, Cheung Pamela, Aguilar Eduardo G, Schneider William M, Bozzacco Leonia, Molina Henrik, Buehler Eugen, Takaoka Akinori, Rice Charles M, Felsenfeld Dan P, MacDonald Margaret R TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP). PLoS pathogens. 2017; 13(1): e1006145.
Li Melody M H, Bozzacco Leonia, Hoffmann Hans-Heinrich, Breton GaÃ«lle, Loschko Jakob, Xiao Jing W, Monette SÃ©bastien, Rice Charles M, MacDonald Margaret R Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion. The Journal of experimental medicine. 2016; 213(13): 2931-2947.
Wang Xinlu, Li Melody M H, Zhao Jing, Li Shenglan, MacDonald Margaret R, Rice Charles M, Gao Xiang, Gao Guangxia Sindbis Virus Can Exploit a Host Antiviral Protein To Evade Immune Surveillance. Journal of virology. 2016; 90(22): 10247-10258.
Li Melody M H, MacDonald Margaret R Polyamines: Small Molecules with a Big Role in Promoting Virus Infection. Cell host & microbe. 2016; 20(2): 123-4.
Bozzacco Leonia, Yi Zhigang, Andreo Ursula, Conklin Claire R, Li Melody M H, Rice Charles M, MacDonald Margaret R Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication. Journal of virology. 2016; 90(6): 3212-28.
Li Melody M H, MacDonald Margaret R, Rice Charles M To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes. Trends in cell biology. 2015; 25(6): 320-9.
Charron Guillaume, Li Melody M H, MacDonald Margaret R, Hang Howard C Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform. Proceedings of the National Academy of Sciences of the United States of America. 2013; 110(27): 11085-90.
Karki Sophiya, Li Melody M H, Schoggins John W, Tian Suyan, Rice Charles M, MacDonald Margaret R Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity. PloS one. 2012; 7(5): e37398.
Li Melody M H, Emerman Michael Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity. Journal of virology. 2011; 85(16): 8197-207.
Li Melody M H, Wu Lily I, Emerman Michael The range of human APOBEC3H sensitivity to lentiviral Vif proteins. Journal of virology. 2010; 84(1): 88-95.
OhAinle Molly, Kerns Julie A, Li Melody M H, Malik Harmit S, Emerman Michael Antiretroelement activity of APOBEC3H was lost twice in recent human evolution. Cell host & microbe. 2008; 4(3): 249-59.