University of Pittsburgh Department of Cell Biology
  • Research

    Many viruses must surmount the barrier presented by the epithelium lining the gastrointestinal tract and/or the endothelium lining the microvasculature to initiate infection and/or facilitate spread. Enteroviruses (coxsackievirus, poliovirus, and echovirus) are transmitted via the fecal-oral route and thus encounter the polarized epithelium lining the gastrointestinal tract early in infection. Following dissemination, the blood-brain barrier (BBB), a structure formed by the polarized endothelial cells lining the vessels surrounding the brain, may have to be breached by enteroviruses to gain entry into the central nervous system (a frequent site of enterovirus secondary infection). Both polarized epithelial and endothelial cells selectively regulate ion and solute flow through the paracellular space and provide a barrier to the migration of pathogens into the interstitium. Nevertheless, enteroviruses have developed strategies to subvert these barriers, as these cells are common sites of enterovirus host infection. Studies in my laboratory focus on two aspects of the interaction(s) between enteroviruses and polarized epithelial and endothelial cells:

    (1) Viral entry . The mechanism(s) by which some enteroviruses breach the barrier presented by the epithelium lining the intestinal tract and the endothelium composing the vasculature and BBB remains poorly understood and are the focus of one area of study in my lab. Our previous studies have established that enteroviruses enter polarized cells by endocytic mechanisms that require activation of specific intracellular signaling molecules that drive actin cytoskeleton reorganization, junctional complex modulation, and eventual virus endocytosis. In ongoing projects in the lab, we utilize a variety of cell biological techniques in order to define the endocytic pathways used by enteroviruses to enter polarized epithelial and endothelial monolayers and to define the intracellular signaling molecules that regulate these processes.

    (2) Innate immunity . Following pathogen assault, the innate immune response initiates mechanisms aimed at clearing the invading pathogen. Our previous studies show that retinoic acid induced gene-I (RIG-I), an intracellular viral recognition molecule, localizes to actin-enriched membrane ruffles in non-polarized epithelial cells and to the apical tight junction complex in cultured intestine epithelial cells and human intestine and colon biopsies. However, it is unclear if the cell biological properties of RIG-I influence pathogen recognition or innate immune signaling. Current studies in the lab focus on characterizing the cell biological properties of innate immune molecules in polarized cells, with a particular focus on RIG-I, to better understand the role of these molecules in innate immune recognition of enteroviruses.

  • Publications

    1. Mukherjee A, Morosky SA, Shen L, Weber CR, Turner JR, Kim KS, Wang T, Coyne CB. Retinoic acid induced gene-1 (RIG-I) associates with the actin cytoskeleton via CARD-dependent interactions. J Biol Chem. 2009 Jan 3. [Epub ahead of print]
    2. Coyne CB, Shen L, Turner JR, Bergelson JM. Coxsackievirus entry across epithelial tight junctions requires occludin and the small GTPases Rab34 and Rab5. Cell Host Microbe. 2007 Sep 13;2(3):181-92.
    3. Coyne CB, Kim KS, Bergelson JM. Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2. EMBO J. 2007 Sep 5;26(17):4016-28. Epub 2007 Aug 23.
    4. Coyne CB, Bergelson JM. Virus-induced Abl and Fyn kinase signals permit coxsackievirus entry through epithelial tight junctions. Cell. 2006 Jan 13;124(1):119-31.


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