The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis
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 ins...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
American Society for Microbiology
2018
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/c0b0e1b8995e4c7fb744b1549803a158 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:c0b0e1b8995e4c7fb744b1549803a158 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:c0b0e1b8995e4c7fb744b1549803a1582021-11-15T15:22:21ZThe Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis10.1128/mSphere.00540-182379-5042https://doaj.org/article/c0b0e1b8995e4c7fb744b1549803a1582018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00540-18https://doaj.org/toc/2379-5042ABSTRACT 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.Svetlana CheferJurgen SeidelAdam S. CockrellBoyd YountJeffrey SolomonKatie R. HagenDavid X. LiuLouis M. HuzellaMia R. KumarElena PostnikovaJ. Kyle BohannonMatthew G. LackemeyerKurt CooperAriel Endlich-FrazierHeema SharmaDavid ThomassonChristopher BartosPhilip J. SayreAmy SimsJulie DyallMichael R. HolbrookPeter B. JahrlingRalph S. BaricReed F. JohnsonAmerican Society for MicrobiologyarticleMERScoronavirusmedical imagingreporter geneMicrobiologyQR1-502ENmSphere, Vol 3, Iss 6 (2018) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
MERS coronavirus medical imaging reporter gene Microbiology QR1-502 |
| spellingShingle |
MERS coronavirus medical imaging reporter gene Microbiology QR1-502 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 The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Svetlana Chefer |
| title |
The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| title_short |
The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| title_full |
The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| title_fullStr |
The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| title_full_unstemmed |
The Human Sodium Iodide Symporter as a Reporter Gene for Studying Middle East Respiratory Syndrome Coronavirus Pathogenesis |
| title_sort |
human sodium iodide symporter as a reporter gene for studying middle east respiratory syndrome coronavirus pathogenesis |
| publisher |
American Society for Microbiology |
| publishDate |
2018 |
| url |
https://doaj.org/article/c0b0e1b8995e4c7fb744b1549803a158 |
| work_keys_str_mv |
AT svetlanachefer thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jurgenseidel thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT adamscockrell thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT boydyount thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jeffreysolomon thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT katierhagen thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT davidxliu thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT louismhuzella thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT miarkumar thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT elenapostnikova thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jkylebohannon thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT matthewglackemeyer thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT kurtcooper thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT arielendlichfrazier thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT heemasharma thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT davidthomasson thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT christopherbartos thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT philipjsayre thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT amysims thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT juliedyall thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT michaelrholbrook thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT peterbjahrling thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT ralphsbaric thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT reedfjohnson thehumansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT svetlanachefer humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jurgenseidel humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT adamscockrell humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT boydyount humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jeffreysolomon humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT katierhagen humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT davidxliu humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT louismhuzella humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT miarkumar humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT elenapostnikova humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT jkylebohannon humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT matthewglackemeyer humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT kurtcooper humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT arielendlichfrazier humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT heemasharma humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT davidthomasson humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT christopherbartos humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT philipjsayre humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT amysims humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT juliedyall humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT michaelrholbrook humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT peterbjahrling humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT ralphsbaric humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis AT reedfjohnson humansodiumiodidesymporterasareportergeneforstudyingmiddleeastrespiratorysyndromecoronaviruspathogenesis |
| _version_ |
1718428031088852992 |