Office Phone: 318-675-4731
Laboratory Phone: 318-675-4732
Office Fax: 318-675-5764
Postdoctoral Fellowship, National Institutes of Health
Ph.D., Virology, 2007, Harvard University B.S., Biochemistry, 1999, University of Wisconsin
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/
Arnold MM. (2018) Rotavirus vaccines: why continued investment in research is necessary. Current Clinical Microbiology Reports 5(1): 73-81.
Lutz LM, Pace CR, Arnold MM. (2016) Rotavirus NSP1 associates with components of the cullin RING ligase family of E3 ubiquitin ligases. Journal of Virology 90(13): 6036-6048.
Arnold MM. (2016) The rotavirus interferon antagonist NSP1: many targets, many questions. Journal of Virology 90(11): 5212-5215. PMID: 27009959.
Arnold MM, 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. PMID: 23824805. PMCID: PMC3754143.
Arnold MM, Sen A, Greenberg HB, Patton JT. (2013) The battle between rotavirus and its host for control of the interferon signaling pathway. PLoS Pathogens 9(1): e1003064. PMID: 23359266. PMCID: PMC3554623.
Arnold MM, Brownback CS, Taraporwala ZF, Patton JT. (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. PMID: 22442114. PMCID: PMC3542736.
Arnold MM, Patton JT. (2011) Diversity of interferon antagonist activities mediated by NSP1 proteins of different rotavirus strains. Journal of Virology 85(5): 1970-1979. PMID: 21177809. PMCID: PMC3067804.
Arnold MM, Patton JT, McDonald S. (2009) Culturing, storage, and quantification of rotavirus. Current Protocols in Microbiology. Nov; Chapter 15:Unit 15C.3. PMID: 19885940. PMCID: PMC3403738.
All Publications: Pubmed