Control theory helps to resolve the measles paradox
Measles virus (MV) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. A crucial challenge in studying MV infection is to understand the so-called ‘measles paradox’—the progression of the infection to severe immunosuppression before clearance of acute virem...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2021-04-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsos.201891 |
| _version_ | 1819063420076425216 |
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| author | Anet J. N. Anelone Edward J. Hancock Nigel Klein Peter Kim Sarah K. Spurgeon |
| author_facet | Anet J. N. Anelone Edward J. Hancock Nigel Klein Peter Kim Sarah K. Spurgeon |
| author_sort | Anet J. N. Anelone |
| collection | DOAJ |
| description | Measles virus (MV) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. A crucial challenge in studying MV infection is to understand the so-called ‘measles paradox’—the progression of the infection to severe immunosuppression before clearance of acute viremia, which is also observed in canine distemper virus (CDV) infection. However, a lack of models that match in vivo data has restricted our understanding of this complex and counter-intuitive phenomenon. Recently, progress was made in the development of a model that fits data from acute measles infection in rhesus macaques. This progress motivates our investigations to gain additional insights from this model into the control mechanisms underlying the paradox. In this paper, we investigated analytical conditions determining the control and robustness of viral clearance for MV and CDV, to untangle complex feedback mechanisms underlying the dynamics of acute infections in their natural hosts. We applied control theory to this model to help resolve the measles paradox. We showed that immunosuppression is important to control and clear the virus. We also showed under which conditions T-cell killing becomes the primary mechanism for immunosuppression and viral clearance. Furthermore, we characterized robustness properties of T-cell immunity to explain similarities and differences in the control of MV and CDV. Together, our results are consistent with experimental data, advance understanding of control mechanisms of viral clearance across morbilliviruses, and will help inform the development of effective treatments. Further the analysis methods and results have the potential to advance understanding of immune system responses to a range of viral infections such as COVID-19. |
| first_indexed | 2024-12-21T15:14:23Z |
| format | Article |
| id | doaj.art-7ff26a62e1534de499e5ebc54e832b82 |
| institution | Directory Open Access Journal |
| issn | 2054-5703 |
| language | English |
| last_indexed | 2024-12-21T15:14:23Z |
| publishDate | 2021-04-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Royal Society Open Science |
| spelling | doaj.art-7ff26a62e1534de499e5ebc54e832b822022-12-21T18:59:11ZengThe Royal SocietyRoyal Society Open Science2054-57032021-04-018410.1098/rsos.201891Control theory helps to resolve the measles paradoxAnet J. N. Anelone0Edward J. Hancock1Nigel Klein2Peter Kim3Sarah K. Spurgeon4School of Mathematics and Statistics, The University of Sydney, Camperdown, New South Wales 2006, AustraliaSchool of Mathematics and Statistics, The University of Sydney, Camperdown, New South Wales 2006, AustraliaDepartment of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UKSchool of Mathematics and Statistics, The University of Sydney, Camperdown, New South Wales 2006, AustraliaDepartment of Electronic and Electrical Engineering, University College London, Torrington Place, London WC1E 7JE, UKMeasles virus (MV) is a highly contagious respiratory morbillivirus that results in many disabilities and deaths. A crucial challenge in studying MV infection is to understand the so-called ‘measles paradox’—the progression of the infection to severe immunosuppression before clearance of acute viremia, which is also observed in canine distemper virus (CDV) infection. However, a lack of models that match in vivo data has restricted our understanding of this complex and counter-intuitive phenomenon. Recently, progress was made in the development of a model that fits data from acute measles infection in rhesus macaques. This progress motivates our investigations to gain additional insights from this model into the control mechanisms underlying the paradox. In this paper, we investigated analytical conditions determining the control and robustness of viral clearance for MV and CDV, to untangle complex feedback mechanisms underlying the dynamics of acute infections in their natural hosts. We applied control theory to this model to help resolve the measles paradox. We showed that immunosuppression is important to control and clear the virus. We also showed under which conditions T-cell killing becomes the primary mechanism for immunosuppression and viral clearance. Furthermore, we characterized robustness properties of T-cell immunity to explain similarities and differences in the control of MV and CDV. Together, our results are consistent with experimental data, advance understanding of control mechanisms of viral clearance across morbilliviruses, and will help inform the development of effective treatments. Further the analysis methods and results have the potential to advance understanding of immune system responses to a range of viral infections such as COVID-19.https://royalsocietypublishing.org/doi/10.1098/rsos.201891measlessliding mode controlbiomedical applications of control engineeringmorbillivirus infectionviral clearanceT-cell immunity |
| spellingShingle | Anet J. N. Anelone Edward J. Hancock Nigel Klein Peter Kim Sarah K. Spurgeon Control theory helps to resolve the measles paradox Royal Society Open Science measles sliding mode control biomedical applications of control engineering morbillivirus infection viral clearance T-cell immunity |
| title | Control theory helps to resolve the measles paradox |
| title_full | Control theory helps to resolve the measles paradox |
| title_fullStr | Control theory helps to resolve the measles paradox |
| title_full_unstemmed | Control theory helps to resolve the measles paradox |
| title_short | Control theory helps to resolve the measles paradox |
| title_sort | control theory helps to resolve the measles paradox |
| topic | measles sliding mode control biomedical applications of control engineering morbillivirus infection viral clearance T-cell immunity |
| url | https://royalsocietypublishing.org/doi/10.1098/rsos.201891 |
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