Michelle M. Arnold , PH.D.


Assistant Professor           

          

Contact Information:                                                                                      

Email:  Office Phone: 318-675-4731
Laboratory Phone: 318-675-4732
Office Fax: 318-675-5764 

Education/Training:

Postdoctoral Fellowship, National Institutes of Health

Ph.D., Virology, 2007, Harvard University

B.S., Biochemistry, 1999, University of Wisconsin

Major Research Interests: Rotavirus-host interactions, innate immune signaling pathways, host antiviral response, ubiquitin-conjugation system

Rotavirus is the leading cause of severe, dehydrating diarrhea in infants and young children, resulting in approximately 500,000 deaths worldwide each year. Most deaths attributable to rotavirus occur in low-income countries where vaccines are not highly effective or widely available. Given the impact of disease caused by rotavirus infections, the understanding of the pathogenesis and host immune response to this virus is surprisingly limited. Rotavirus infection triggers complex signaling cascades that result in interferon (IFN) induction and antiviral gene expression by the host cell. Expression of the nonstructural protein NSP1 prevents the induction of IFN by promoting the degradation of the transcription factors IRF3, IRF5 and/or IRF7. The host proteins targeted by NSP1 vary between different rotavirus strains, a common theme among viruses that circulate as different types or strains. This flexibility may play a role in host specificity or strain virulence.

My lab is interested in understanding the mechanism of NSP1 activity, which is hypothesized to induce protein degradation by acting as an E3 ubiquitin ligase. We are also interested in elucidating additional functions of NSP1 and determining if there are other rotavirus proteins that interfere with innate host responses. Viruses containing gene deletions that prevent expression of IFN antagonists are good candidates for next-generation vaccines, but developing successful vaccines will depend upon understanding the molecular mechanisms of IFN antagonism.

Laboratory Webpage: http://www.arnoldvirology.org/

 

Representative Publications:

Arnold M.M. (2013) Sequestration strikes again: rotavirus-induced accumulation of cellular transcripts in the nucleus inhibits host protein translation. Future Virology 8(9): 841-844.

 

Arnold M.M., Barro M, Patton JT. (2013) Rotavirus NSP1 mediates degradation of interferon regulatory factors through targeting of the dimerization domain. Journal of Virology 87(17): 9813-9821.

Arnold M.M., Sen A., Greenberg H.B., Patton J.T. 2013. The battle between rotavirus and its host for control of the interferon signaling pathway. PLoS Pathogens 9(1): e1003064. 

Arnold M.M., Brownback C.S., Taraporwala Z.F., Patton J.T. 2012 Rotavirus variant replicates efficiently although encoding an aberrant NSP3 that fails to induce nuclear localization of poly-A binding protein. Journal of General Virology. 93(7): 1483-1494.

Arnold M.M., and Patton J.T. 2011. Diversity of interferon antagonist activities mediated by NSP1 proteins of different rotavirus strains. Journal of Virology 85(5): 1970-1979.

Arnold M.M., and Patton J.T. 2009. Rotavirus antagonism of the innate immune response. Viruses. 1(3): 1035-1056.

Arnold M.M., Patton J.T., and McDonald S. 2009. Culturing, storage, and quantification of rotavirus. Current Protocols in Microbiology. Nov; Chapter 15:Unit 15C.3.

 

All Publications: Pubmed