Anthony Fehr

Postdoctoral Research FellowAnthony Fehr
Address: 3-730 BSB
Phone: (319) 335-7576
Email: anthony-fehr@uiowa.edu

Mentor: Stanley Perlman, MD, PhD

Undergraduate Institution: University of Nebraska-Lincoln

PhD Institution: Washington University-St Louis

Research Description

Coronaviruses are a family of large, positive-sense RNA viruses that cause a wide variety of diseases in humans and veterinary animals. These are highlighted by SARS-CoV and MERS-CoV that have caused recent outbreaks of severe human disease. In addition, Coronaviruses such as PEDV and IBV cause significant disease and economic loss in the agriculture industry. My work is focused on ADP-ribosylation and its impact on Coronaviruses and the innate immune response. All Coronaviruses encode for a macrodomain protein that can remove ADP-ribose from target proteins. To study ADP-ribosylation in the context of a Coronavirus infection, we have created recombinant Coronaviruses with mutations in the catalytic domain of the macrodomain and are thus unable to remove ADP-ribose from proteins. These mutations dramatically reduce the ability of CoVs to cause disease. In addition, we have found that the macrodomain represses IFN production and promotes in vivo replication of Coronaviruses. We are currently addressing whether PARPs, the enzymes that add ADP-ribose to proteins, are antiviral in the absence of macrodomain activity. If they are, one of our goals will be to identify the specific anti-viral PARP that is responsible for this effect. Furthermore, we are beginning to address what proteins may be ADP-ribosylated during infection and targeted by the macrodomain. In the future, we will determine whether the macrodomain may be a suitable therapeutic target to reduce CoV disease and to use these mutant viruses as a platform to develop novel live-attenuated vaccines for a number of Coronavirus infections. I am also interested in identifying additional viral factors that impact the innate immune response during infection.

Publication(s)

J. Athmer, A.R. Fehr, M. Grunewald, E.C. Smith, M.R. Denison, and Stanley Perlman. 2017. In situ tagged nsp15 reveals nsp15 interactions with Coronavirus replication/ transcription complex associated proteins. mBio 8:emBio.02320-16.

A.R. Fehr, R. Channappanavar, G. Jankevicious, C. Fett, J. Zhao, J. Athmer, D. K. Meyerholz, Ivan Ahel, and Stanley Perlman. 2016. The conserved coronavirus macrodomain promotes virulence and suppresses the innate immune response during severe acute respiratory syndrome coronavirus infection. mBio 7(6):e01721-16. doi:10.1128/mBio.01721-16.

J.E. Park, K. Li, A. Barlan, A.R. Fehr, S. Perlman, P.B. McCray, and T. Gallagher. 2016. Proteolytic Processing of Middle East Respiratory Syndrome Coronavirus Spike Proteins Expands Virus Tropism. Proc Natl Acad Sci. doi:10.1073

R. Channappanavar, A.R. Fehr, R. Vijay, M. Mack, J. Zhao, D.K. Meyerholz, and S. Perlman. 2016. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host & Microbe 19:181-193.

A.R. Fehr, J. Athmer, R. Channappanavar, J.M. Phillips, D.K. Meyerholz, and S. Perlman. 2015. The nsp3 macrodomain promotes virulence in mice with coronavirus-induced encephalitis. J Virol. 89:1523-1536. [Featured in JVI Spotlight]

N. Caffarelli*, A.R. Fehr*, 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.

E. Lauron, 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.

T.C. Chapa, 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.

A.R. Fehr, Gualberto N. C., Savaryn J.P., Terhune S.S., and Yu D. 2012. Proteasome-dependent disruption of the E3 ubiquitin ligase anaphase-promoting complex by HCMV protein pUL21a. PLoS Pathog. 8(7): e1002789.

Y. Perng, Z. Qian, A.R. Fehr, B. Xuan, and D. Yu. 2011. Human cytomegalovirus gene UL79 is required for the accumulation of late viral transcripts. J Virol. 85:4841-52.

A.R. Fehr 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.

E.L. Fuchs, 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. 192:2779-90.

A.R. Fehr 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.

Review articles

A.R. Fehr*, R. Channapannavar* and S. Perlman. 2017. Middle East Respiratory Syndrome: Emergence of a pathogenic human coronavirus. Annu. Rev. Med. 2017. 68:387-99
*These authors contributed equally to this manuscript.

A.R. Fehr and S. Perlman. 2015. Coronaviruses: An overview of their replication and pathogenesis. Methods Mol. Biol. 1282:1-23.

A.R. Fehr 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)]

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