The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis
Svetlana Chefer,
Jurgen Seidel,
Adam S. Cockrell,
Boyd Yount,
Jeffrey Solomon,
Katie R. Hagen,
David X. Liu,
Louis M. Huzella,
Mia R. Kumar,
Elena Postnikova,
J. Kyle Bohannon,
Matthew G. Lackemeyer,
Kurt Cooper,
Ariel Endlich-Frazier,
Heema Sharma,
David Thomasson,
Christopher Bartos,
Philip J. Sayre,
Amy Sims,
Julie Dyall,
Michael R. Holbrook,
Peter B. Jahrling,
Ralph S. Baric,
Reed F. Johnson
Affiliations
Svetlana Chefer
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Jurgen Seidel
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Adam S. Cockrell
Department of Epidemiology, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina, USA
Boyd Yount
Department of Epidemiology, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina, USA
Jeffrey Solomon
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA
Katie R. Hagen
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
David X. Liu
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Louis M. Huzella
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Mia R. Kumar
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Elena Postnikova
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
J. Kyle Bohannon
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Matthew G. Lackemeyer
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Kurt Cooper
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Ariel Endlich-Frazier
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Heema Sharma
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
David Thomasson
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Christopher Bartos
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Philip J. Sayre
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Amy Sims
Department of Epidemiology, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina, USA
Julie Dyall
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Michael R. Holbrook
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Peter B. Jahrling
Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
Ralph S. Baric
Department of Epidemiology, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina, USA
Reed F. Johnson
Emerging Viral Pathogens Section, Laboratory of Immunoregulation, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA
ABSTRACT Single photon emission computed tomography (SPECT) is frequently used in oncology and cardiology to evaluate disease progression and/or treatment efficacy. Such technology allows for real-time evaluation of disease progression and when applied to studying infectious diseases may provide insight into pathogenesis. Insertion of a SPECT-compatible reporter gene into a virus may provide insight into mechanisms of pathogenesis and viral tropism. The human sodium iodide symporter (hNIS), a SPECT and positron emission tomography reporter gene, was inserted into Middle East respiratory syndrome coronavirus (MERS-CoV), a recently emerged virus that can cause severe respiratory disease and death in afflicted humans to obtain a quantifiable and sensitive marker for viral replication to further MERS-CoV animal model development. The recombinant virus was evaluated for fitness, stability, and reporter gene functionality. The recombinant and parental viruses demonstrated equal fitness in terms of peak titer and replication kinetics, were stable for up to six in vitro passages, and were functional. Further in vivo evaluation indicated variable stability, but resolution limits hampered in vivo functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease. IMPORTANCE Advanced medical imaging such as single photon emission computed tomography with computed tomography (SPECT/CT) enhances fields such as oncology and cardiology. Application of SPECT/CT, magnetic resonance imaging, and positron emission tomography to infectious disease may enhance pathogenesis studies and provide alternate biomarkers of disease progression. The experiments described in this article focus on insertion of a SPECT/CT-compatible reporter gene into MERS-CoV to demonstrate that a functional SPECT/CT reporter gene can be inserted into a virus.
