Undergraduate Institution: University of Nebraska-Lincoln

PhD Institution: Washington University-St Louis

Research Description

I am interested in the role of the ADRP (ADP-ribose 1' phosphatase) domain encoded within nsp3 of both Severe Acute Respiratory Syndrome (SARS)-Coronavirus and Murine Hepatitis Virus (MHV). This domain is known to have enzymatic activity and binds ADP-ribose however it is still unclear how these activities would affect viral replication and/or pathogenesis. It has previously been shown that this domain is important for pathology of the liver during MHV infection, however its role in brain pathology caused by MHV or during SARS infection of mice has not yet been examined. We are using a variety of novel genetic tools including Bacterial Artificial Chromosome (BAC) technology to create specific point mutations within the ADRP domain and address these questions. Ultimately we hope to identify the host proteins which interact with this domain and the mechanism it uses to cause pathogenesis.

Publication(s)

Fehr A.R. and S. Perlman. 2014. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol. Biol. 1282:1-23.

Fehr A.R., J. Athmer, R. Channappanavar, J.M. Phillips, D.K. Meyerholz, and S. Perlman. 2014. The NSP3 macrodomain promotes virulence in mice with coronavirus-induced encephalitis. J Virol. 89:1523-1536. [Featured in JVI Spotlight]

Fehr A.R. and D. Yu. 2013. Control the host cell cycle: viral regulation of the anaphase-promoting complex. J Virol. 87:8818-8825. [Featured on Global Medical Discovery (ISSN 1929-8536)]

Caffarelli N.*, Fehr A.R.*, and Yu D. (2013) Cyclin A degradation by primate cytomegalovirus protein pUL21a counters Its innate restriction of virus replication. PLoS Pathog 9(12): e1003825.*These authors contributed equally to this manuscript.

Lauron E., D. Yu, A.R. Fehr, and L. Hertel. 2013. Human cytomegalovirus infection of Langerhans-type dendritic cells does not require the presence of the gH/gL/UL128-131A complex and is blocked after nuclear deposition of viral genomes in immature cells. J Virol. 88:403-416.

Chapa T.C., S. Johnson, C. Affolter, M.C. Valentine, A.R. Fehr, W.M. Yokoyama, and D. Yu. 2013. Murine cytomegalovirus protein pM79 is a key regulator for viral late transcription. J Virol. 87:9135-9147.

Fehr A.R., N.C. Gualberto, J.P. Savaryn, S.S. Terhune, and D. Yu. (2012) Proteasome-Dependent Disruption of the E3 Ubiquitin Ligase Anaphase-Promoting Complex by HCMV Protein pUL21a. PLoS Pathog 8(7): e1002789. doi:10.1371/journal.ppat.1002789

Fehr A.R. and D. Yu. 2011. Human cytomegalovirus early protein pUL21a facilitates efficient viral DNA synthesis and the late accumulation of immediate-early transcripts. J Virol. 85:663-674.

Perng Y., Z. Qian, A.R. Fehr, B. Xuan, and D. Yu. 2 March 2011. Human cytomegalovirus gene UL79 is required for the accumulation of late viral transcripts. J Virol. doi:10.1128/JVI.02344-10

Fuchs E.L., E.D. Brutinel, E.R. Klem, A.R. Fehr, T.L. Yahr, and M.C. Wolfgang. 2010. In vitro and in vivo characterization of the Pseudomonas aeruginosa cyclic AMP (cAMP) phosphodiesterase CpdA, required for cAMP homeostasis and virulence factor regulation. J Bacteriol. 192(11):2779-90.

Fehr A.R. and D. Yu. 2010. Human cytomegalovirus gene UL21a encodes a short-lived cytoplasmic protein and facilitates virus replication in fibroblasts. J Virol. 84:291-302.

Award(s)

• Regents Scholar, University of Nebraska-Lincoln, 2001-2005
• Honors Program, University of Nebraska-Lincoln, 2001-2005
• Morse/Berg Fellowship, Department of Molecular Microbiology, Washington University-St Louis, 2008
• Milton and Sondra Schlesinger Student Travel Award, Department of Molecular Microbiology, Washington University-St Louis, 2008
• Infectious Disease Fellowship, Department of Infectious Diseases, Washington University-St Louis, 2008-2010
• David M. Kipnis Thesis Award, Department of Developmental Biology, Washington University-St Louis, 2011
• International Herpesvirus Workshop Phase I Travel Award, 2011
• T32 Postdoctoral Fellowship, Center for Immunology, University of Iowa, 2013
• F32 Ruth Kirschstein NRSA Postdoctoral Fellowship, NIH, 2014
• Travel Award, Levitt Center for Virology, University of Iowa, 2014
• ASV Postdoctoral Fellow Travel Award, 2015