Microbiology, Immunology & Molecular Genetics Faculty
Xiangzhi Meng, M.D.,Ph.D.
Ph.D. National Institute for Viral Disease Control and Prevention, Chinese center for Disease Control and Prevention.
MD. Jining Medical University, Shandeigh, P.R. China
Keywords: Vaccinia Virus; Pox virus
Dr. Meng's lab focuses primarily on vaccinia virus. Vaccinia virus is the protypical pox virus and serves as the vaccine for smallpox. Poxviruses included some dangerous emerging or re-emerging pathogens as well as some promising vaccine vectors for infectious diseases and cancers.
Poxviruses are unique among viruses in that they encode a large number of proteins that are dedicated to evading host immune responses. These proteins include secreted inhibitors of cytokines as well as intracellular inhibitors of immune signaling or antiviral factors. A major goal of Dr. Men's laboratory is to uncover the mechanisms of pox virus immune evasion, which will reveal fundamental principles about virus-host interactions and provide knowledge for the development of vaccines and antivirals. They are studying several pox virus immune evasion molecules, including a secreted pox virus interleukin-18 (IL-18) binding protein, which prevents IL-18 from inducing interferon-y production, and two intracellular inhibitors of type I interferons, K1 and C7. K1 and C7 are also host-range factors essential for poxviruses replication in mammalian hosts and have been manipulated to generate safe vaccine vector. They are studying these pox virus immune evasion molecules by using a multidisciplinary approach, including molecular virology, immunology, and protein crystallography.
Another focus of the laboratory is to decipher the complex cellular process involved in assembling vaccinia virus virions. Vaccinia virions are assembled in the cytoplasm within "virus factories" and require the biogenesis of lipid virion envelope from cellular organelles. They have recently discovered a group of nonstructural viral proteins that play essential and non-redundant roles in virion membrane biogenesis. They are currently using molecular genetics, biophysics, and cell-biology approaches to determine how these viral proteins work cooperatively to generate virion membranes. This will provide insight on how cellular membrane organelles are generated or re-organized in the cells, which are normal cellular processes often manipulated by pathogens.
- Meng X, Wu X, Yan B, Deng J, Xiang Y. Analysis of the role of vaccinia virus H7 in virion membrane biogenesis with an H7-deletion mutant. J Virol. 2013 May 15. [Epub ahead of print] PMID: 23678177.
- Benhnia MR, Maybeno M, Blum D, Aguilar-Sino R, Matho M, Meng X, Head S, Felgner PL, Zajonc DM, Koriazova L, Kato S, Burton DR, Xiang Y, Crowe JE Jr, Peters B, Crotty S. J. Unusual features of vaccinia virus extracellular virion form neutralization resistance revealed in human antibody responses to the smallpox vaccine. J Virol. 2013 Feb;87(3):1569-85. doi: 10.1128/JVI.02152-12. Epub 2012 Nov 14.
- Meng X, Rose L, Xiang Y. 2012. Mechanisms of Interferon Antagonism by Poxviruses. In Nucleic Acid Sensors and Antiviral Immunity, edited by Suryaprakash Sambhara and Takashi Fujita. 2012 Landes Bioscience. http://www.landesbioscience.com/books/iu/id/4288/
- Krumm B, Meng X, Wang Z, Xiang Y, Deng J. A unique bivalent binding and inhibition mechanism by the yatapoxvirus interleukin 18 binding protein. PLoS Pathog. 2012;8(8):e1002876. doi: 10.1371/journal.ppat.1002876. Epub 2012 Aug 23.
- Wu X, Meng X, Yan B, Rose L, Deng J, Xiang Y.Vaccinia virus virion membrane biogenesis protein A11 associates with viral membranes in a manner that requires the expression of another membrane biogenesis protein, A6. J Virol. 2012 Oct;86(20):11276-86.
- Meng X, Xiang Y. Generation and characterization of monoclonal antibodies specific for vaccinia virus. Methods Mol Biol. 2012;890:219-32. doi: 10.1007/978-1-61779-876-4_13.
- Matho MH, Maybeno M, Benhnia MR, Becker D, Meng X, Xiang Y, Crotty S, Peters B, Zajonc DM.Structural and biochemical characterization of the vaccinia virus envelope protein D8 and its recognition by the antibody LA5. J Virol. 2012 Aug;86(15):8050-8. doi: 10.1128/JVI.00836-12. Epub 2012 May 23.
- Meng X, Embry A, Rose L, Yan B, Xu C,Xiang Y. Vaccinia Virus A6 is Essential for Virion Membrane Biogenesis and Localization of Virion Membrane Proteins to Sites of Virion Assembly. J Virol. 2012 May;86(10):5603-13. doi: 10.1128/JVI.00330-12. Epub 2012 Mar 7.
- Meng X, Schoggins J, Rose L, Cao J, Ploss A, Rice CM,Xiang Y. C7L Family of Poxvirus Host-range Genes Inhibit Antiviral Activities Induced by Type I Interferons and Interferon Regulatory Factor 1. J Virol. 2012 Apr;86(8):4538-47. doi: 10.1128/JVI.06140-11. Epub 2012 Feb 15.
- Xu C, Meng X, Yan B, Crotty S, Deng J,Xiang Y. An epitope conserved in orthopoxvirus A13 envelope protein is the target of neutralizing and protective antibodies. Virology. 2011 Sep 15;418(1):67-73. Epub 2011 Aug 2.