个人简介

B.S. Wuhan University, Wuhan, China, 1982 Ph.D. Purdue University, West Lafayette, IN, 1987 Biochemistry, Biophysical Chemistry

研究领域

Biochemistry, Biophysical Chemistry

The genome of viruses has a limited size that usually is only sufficient to encode a few viral proteins. To assemble a fully functional virion, the viral capsid applies simple symmetry to build the viral particle with multiple copies of the same protein subunit. This universal principle is found in virus structures through the entire virosphere. Influenza virus (IFV) continues to be a major health problem around the world. The underlining reason that IFV continues to be a major health threat is directly related to its structure. IFV is an enveloped virus that has 8 RNA segments as its genome. The segmented RNA genome is in negative sense and encodes 10 different viral proteins. The segmented organization of IFV genome allows re-assortment between IFVs from different species to occur. As the result, new IFV that contains gene segments never found in IFVs that infect humans can emerge through re-assortment. We are working on IFV proteins, including the matrix protein M1, the ribonucleoprotein NP and the polymerase, to delineate the role of these proteins in re-assortment and virulence. Moreover, we are also using structure-aided approaches to design novel antiviral drugs to treat IFV infection in humans. In the past, we have developed licensed an antiviral drug targeting neuraminidase (NA) that is a viral protein on the surface of IFV. NA inhibitors block virus release so the newly produced virions could not infect other cells. While continuing to improve the pharmacological properties of NA inhibitors, we are also making efforts to identify inhibitors of other viral proteins. On a larger scale, the replication mechanism of negative strand RNA viruses (NSVs) is unique among all biological systems. NSVs include a number of important viral pathogens, such as respiratory syncytial virus (RSV), parainfluenza virus (PIV), mumps virus (MuV) and Ebola virus (EBV). The one factor that separates NSVs from others is that the template for viral RNA synthesis is not the genomic RNA alone, but the nucleocapsid that is formed by encapsidation of viral genomic RNA with the nucleocapsid protein. During the viral RNA synthesis, the virus-coded RNA polymerase must recognize the nucleocapsid and gain access to the sequestered RNA sequence inside the nucleocapsid in order to use it as the template for copying the RNA sequence. We have solved the structure of a large number of viral proteins and developed the new paradigm for viral RNA synthesis of NSVs. Our efforts continue to unveil the molecular mechanism of NSV replication, with an emphasis on the structure of the large subunit L in the viral polymerase.

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Green TJ, Zhang X, Wertz GW, Luo M. “Structure of the vesicular stomatitis virus nucleoprotein-RNA complex”. Science. 2006 Jul 21;313(5785):357-60. PMID: 16778022 Green TJ, Luo M. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11713-8. PMID: 19571006 Ge P, Tsao J, Schein S, Green TJ, Luo M, Zhou ZH. Cryo-EM model of the bullet-shaped vesicular stomatitis virus. Science. 2010 Feb 5;327(5966):689-93. PMID: 20133572 Cox R, Green TJ, Purushotham S, Deivanayagam C, Bedwell GJ, Prevelige PE, Luo M. Structural and functional characterization of the mumps virus phosphoprotein. J Virol. 2013 Jul;87(13):7558-68. doi: 10.1128/JVI.00653-13. Epub 2013 May 1. PMID: 23637399 Green TJ, Cox R, Tsao J, Rowse M, Qiu S, Luo M. Common mechanism for RNA encapsidation by negative strand RNA viruses. J Virol. 2014 Apr;88(7):3766-75. doi: 10.1128/JVI.03483-13. Epub 2014 Jan 15. PMID: 24429372