Research | Publications | Lab Members
Yan Xiang, Ph.D.
Room 4.031V Tel: (210) 567-0884Fax: (210) 567-6612Email:
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.
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