The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis

mSphere

Jeffrey Solomon¹  Adam S. Cockrell²  Ralph S. Baric²  Boyd Yount²  Amy Sims²  Reed F. Johnson³  Mia R. Kumar³  Heema Sharma³  Ariel Endlich-Frazier³  Peter B. Jahrling⁴  Svetlana Chefer⁴  Elena Postnikova⁴  Christopher Bartos⁴  Julie Dyall⁴  David Thomasson⁴  Katie R. Hagen⁴  Louis M. Huzella⁴  J. Kyle Bohannon⁴  Matthew G. Lackemeyer⁴  Kurt Cooper⁴  Jurgen Seidel⁴  Michael R. Holbrook⁴  Philip J. Sayre⁴  David X. Liu⁴ 

[1] Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA;Department of Epidemiology, University of North Carolina—Chapel Hill, Chapel Hill, North Carolina, USA;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;Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA;

关键词: MERS;    coronavirus;    medical imaging;    reporter gene;   

DOI  :  10.1128/mSphere.00540-18

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown