Tem Morrison

Assistant Professor Ph.D., University of North Carolina

Current Research

Molecular pathogenesis of arbovirus infection and regulation of virus-induced inflammatory responses Current Research The major interest of the laboratory is the molecular pathogenesis of viral infection, with an emphasis on mosquito-transmitted viruses. Mosquito-transmitted viruses include flaviviruses, such as Dengue virus and West Nile virus, bunyaviruses, such as Rift Valley fever virus, and alphaviruses, such as chikungunya virus and Ross River virus. Chikungunya virus and Ross River virus are a cause of debilitating arthritis and myositis in humans and these viruses are capable of initiating explosive epidemics that can involve thousands to millions of infected patients and are an emerging disease threat. My research utilizes mouse models based on chikungunya virus or Ross River virus infection to investigate host and viral factors that contribute to immunopathologic inflammation and disease. These mouse models enable us to utilize transgenic and knockout strains to study the role of specific host genes in the disease process and investigate the genetics of host susceptibility to infection. Additionally, due to the well-established alphavirus reverse genetics system, we are able to easily manipulate the genome of the virus. Taken together, these advantages provide a highly tractable system to establish mechanisms by which viral interactions with the host lead to disease. In terms of host factors, we have recently discovered that multiple components of the host complement system contribute to Ross River virus-induced tissue injury at the sites of inflammation. Activation of the complement system generates a number of ligands that interact with receptors expressed by inflammatory leukocytes. Currently, we are investigating the role of complement receptors in Ross River virus and chikungunya virus pathogenesis, complement receptor regulation of leukocyte activation and effector function, and the contribution of complement regulated effectors to virus-induced inflammatory disease. On the virus side, studies are focused on identifying viral genetic determinants that promote the severe host inflammatory response. Towards that goal, we have identified a strain of Ross River virus that fails to initiate inflammation and disease in the mouse model, yet viral loads in tissues and viral tissue tropism are remarkably similar to the virulent strain. A panel of chimeric viruses is being utilized to identify specific viral genetic determinants associated with the development of disease and investigate how those determinants interact with the host to promote inflammation.

Recent Publications

O’Brien, K.B., Morrison, T.E., Gendron-Fitzpatrick, A., Dundore, D.Y., Heise, M.T., and Schultz-Cherry, S. 2009.  A protective role for complement C3 protein during H5N1 avian influenza virus infection.  Manuscript submitted. 

Morrison, T.E., Simmons, J.D., and Heise, M.T. 2008. CR3 (CD11b/CD118) promotes severe Ross River virus-induced inflammatory disease. In press. J. Virol.

Moore, C.B., Bergstralh, D.T., Duncan, J.A., Lei, Y., Morrison, T.E., Zimmerman, A.G., Accavitti-Loper, M.A., Madden, V.J., Sun, L.,Ye, Z., Lich, J.D., Heise, M.T., Chen, Z., and Ting, J.P.-Y. 2008. NLRX1 is a regulator of mitochondrial antiviral immunity. Nature 451, 573-575.

Morrison, T.E. and Heise, M.T. 2008. The host complement system and arbovirus pathogenesis. Curr. Drug Targets 9, 165-72. Morrison T.E., Fraser R.J., Smith P.N., Mahalingam S., and Heise MT. 2007. Complement contributes to inflammatory tissue destruction in a mouse model of Ross River virus-induced disease. J. Virol. 81, 5132-43.

Shabman R.S., Morrison T.E., Moore C., White L., Suthar M.S., Hueston L., Rulli N., Lidbury B., Ting J.P., Mahalingam S., and Heise M.T. 2007. Differential induction of type I interferon responses in myeloid dendritic cells by mosquito and mammalian-cell-derived alphaviruses. J. Virol. 81, 237-247.

Morrison, T.E., Whitmore, A.C., Shabman, R.S., Lidbury, B.A., Mahalingam, S, and Heise, M.T. 2006. Characterization of Ross River virus tropism and virus-induced inflammation in a mouse model of viral arthritis and myositis. J. Virol. 80, 737-749.

Morrison, T.E., and Kenney, S.C. 2004. BZLF1, an Epstein-Barr virus immediate-early protein, induces p65 nuclear translocation while inhibiting p65 transcriptional function. Virology 328, 219-232.

Hong, G.K., Delecluse H.J., Gruffat, H., Morrison, T.E., Feng W.H., Sergeant, A., and Kenney, S.C. 2004. The BRRF1 early gene of Epstein-Barr virus encodes a transcription factor that enhances induction of lytic infection by BRLF1. J. Virol. 78, 4983-4992.

Morrison, T.E., Mauser, A., Klingelhutz, A., and Kenney, S.C. 2004. The Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor-α induced signaling and apoptosis by downregulating tumor necrosis factor receptor-1. J. Virol. 78, 544-549.

Morrison, T.E., Mauser, A., Wong, A., Ting, J. P.-Y., and Kenney, S.C. 2001. Inhibition of IFN-γ signaling by an Epstein-Barr virus immediate-early protein. Immunity 15, 787-799.