Microbiology & Immunology Faculty
Yan Xiang, Ph.D.
The primary interest of our laboratory is host-pathogen interactions, with poxviruses as our model systems.
Variola virus and molluscum contagiosum virus (MCV) are the only two members of poxvirus family that exclusively infect humans and cause human diseases. Variola virus is the causative agent of smallpox. A closely related poxvirus, vaccinia virus, serves as the vaccine for smallpox. However, the vaccination causes a relatively high level of immunization complications. MCV is still prevalent throughout the world. Unlike smallpox virus, MCV causes small, benign skin lesions in children and young adults and a more extensive disease only when there is a concurrent immunodeficiency such as AIDS. We are trying to understand the molecular mechanisms of poxviral pathogenesis by uncovering the functions of various poxviruses virulence factors.
Some of the poxviral virulent factors are soluble or membrane-bound proteins that directly modulate the host immune response. The discovery and characterization of these proteins provide insights into the mechanisms of viral pathogenesis as well as the functions of the host immune system. A new strategy of immune modulation was recently revealed by the discovery of a soluble interleukin-18 binding protein (IL-18BP) in poxviruses and their mammalian hosts. Interleukin-18 (IL-18) is a proinflammatory cytokine that can enhance both the innate and acquired immunity. IL-18 protects against microbial infection and tumors in murine models. Excessive IL-18 activities, however, are associated with many autoimmune and inflammatory diseases. The poxvirus and host IL-18BPs can bind to IL-18 with high affinities and inhibit IL-18 mediated IFN-gamma induction. Therefore, IL-18, IL-18BP and their mimetics are all potentially important therapeutic agents. We are continuing our studies on IL-18BP and are getting a detailed understanding of the specific interactions between IL-18 and its binding partners by using a combination of methods including sequence comparison, structural modeling, mutagenesis and quantitative molecular interaction.
- 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.
- Embry A, Meng X, Cantwell A, Dube PH, Xiang Y. Enhancement of immune response to an antigen delivered by vaccinia virus by displaying the antigen on the surface of intracellular mature virion. Vaccine. 2011 Jul 26;29(33):5331-9. Epub 2011 Jun 12.
- Meng X, Zhong Y, Embry A, Yan B, Lu S, Zhong G, Xiang Y. Generation and characterization of a large panel of murine monoclonal antibodies against vaccinia virus. Virology. 2011 Jan 20;409(2):271-9. Epub 2010 Nov 5.
- Li Y, Meng X, Xiang Y, Deng J. Structure function studies of vaccinia virus host range protein k1 reveal a novel functional surface for ankyrin repeat proteins. . J Virol. 2010 Apr;84(7):3331-8. Epub 2010 Jan 2.
- Willis KL, Patel S, Xiang Y, Shisler JL. The effect of the vaccinia K1 protein on the PKR-eIF2alpha pathway in RK13 and HeLa cells . Virology. 2009 Nov 10;394(1):73-81. Epub 2009 Sep 9.
- Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, Bose S. Activation of innate immune antiviral responses by Nod2. Nature Immunology. 10, 1073 - 1080 (2009)
- Xiangzhi Meng, Canhua Jiang, Janilyn Arsenio, Jingxin Cao, Yan Xiang. Vaccinia Virus K1L and C7L Inhibit Antiviral Activities Induced by Type-I Interferons . J Virol. 2009 Oct;83(20):10627-36. Epub 2009 Aug 5.
Krumm B, Meng X, Li Y, Xiang Y, Deng J. 2008. Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein.
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20711-5. Epub 2008 Dec 22.
- Nazarian SH, Rahman MM, Werden SJ, Villeneuve D, Meng X, Brunetti C, Valeriano C, Wong C, Singh R, Barrett JW, Xiang Y and McFadden G. 2008. Yaba monkey tumor virus encodes a functional inhibitor of interleukin-18. J. Virol. 82(1):522-8.
- Meng X, Chao J and Xiang Y. 2007. Identification from diverse mammalian poxviruses of host-range regulatory genes functioning equivalently to vaccinia virus C7L. Virology. 2008 Mar 15;372(2):372-83. Epub 2007 Dec 3.
- Meng X, Embry A, Sochia D and Xiang Y. 2007. Vaccinia Virus A6L Encodes a Virion Core Protein Required for Formation of Mature Virion. J. Virol. 81(3):1433-43.
- Meng X, Leman M and Xiang Y. 2007. Variola virus IL-18 binding protein interacts with three human IL-18 residues that are part of a binding site for human IL-18 receptor alpha subunit. Virology. 358(1):211-20.
- Basu M, Maitra RK, Xiang Y, Meng M, Banerjee AK and Bose S. 2006. Inhibition of vesicular stomatitis virus infection in epithelial cells by alpha interferon-induced soluble secreted proteins. J Gen Virol. 87(Pt9):2653-2662.
- Meng X and Xiang Y. 2006. Vaccinia virus K1L protein supports viral replication in human and rabbit cells through a cell-type-specific set of its ankyrin repeat residues that are distinct from its binding site for ACAP2. Virology. 353(1):220-233.
- Xiang Y and Moss B. 2003. Molluscum contagiosum virus interleukin-18 (IL-18) binding protein is secreted as a full-length form that binds cell surface glycosaminoglycans through the C-terminal tail and a furin-cleaved form with only the IL-18 binding domain. J. Virol. 77(4):2623-30.
- Xiang Y and Moss B. 2001. Correspondence of the Functional Epitopes of Poxvirus and Human IL-18 Binding Proteins. J. Virol. 75(20):9947-54.
- Xiang Y and Moss B. 2001. Determination of the Functional Epitopes of Human IL-18 Binding Protein by Site-Directed Mutagenesis. J. Biol. Chem. 276(20):17380-6.
- Calderara S., Xiang, Y and Moss, B. 2001. Orthopoxvirus IL-18 binding proteins: affinities and antagonist activities. Virology. 279:22-26.
- Moss B, Shisler JL, Xiang Y and Senkevich TG. 2000. Immune-defense molecules of molluscum contagiosum virus, a human poxvirus. Trends Microbiol. 8(10):473-7.
- Xiang Y and Moss B. 1999. IL-18 binding and inhibition of interferon gamma induction by human poxvirus-encoded proteins. Proc. Natl. Acad. Sci. USA. 96:11537-42.
- Xiang Y and Moss B. 1999. Identification of human and mouse homologs of the MC51L-53L-54L family of secreted glycoproteins encoded by the Molluscum contagiosum poxvirus. Virology 257:297-302.
- Xiangzhi Meng, MD, Ph.D., Assistant Professor/Research
- Bo Yan
- Guohua Wu