Abstract
BackgroundThe pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. 18F-Fluorodeoxyglucose ([18F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [18F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. We used [18F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (Ki) in responsive lymphoid tissue.MethodsMultiple [18F]-FDG-PET and CT images were acquired on a PET/CT clinical scanner modified to operate in a biosafety level 4 environment prior to and up to 29 days after MERS-CoV aerosol exposure. Time activity curves of various lymphoid tissues were reconstructed to follow the [18F]-FDG uptake for approximately 60 min (3,600 s). Image-derived input function was used to calculate Ki for lymphoid tissues by Patlak plot.ResultsTwo-way repeated measures analysis of variance revealed alterations in Ki that was associated with the time point (p < 0.001) after virus exposure and the location of lymphoid tissue (p = 0.0004). As revealed by a statistically significant interaction (p < 0.0001) between these two factors, the pattern of Ki changes over time differed between three locations but not between subjects. A distinguished pattern of statistically significant elevation in Ki was observed in mediastinal lymph nodes (LNs) that correlated to Ki changes in axillary LNs. Changes in LNs Ki were concurrent with elevations of monocytes in peripheral blood.Conclusions[18F]-FDG-PET is able to detect subtle changes in host immune response to contain a subclinical virus infection. Full quantitative analysis is the preferred approach rather than semiquantitative analysis using standardized uptake value for detection of the immune response to the virus.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0143-x) contains supplementary material, which is available to authorized users.
Highlights
The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. 18F-Fluorodeoxyglucose ([18F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [18F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging
Nonhuman primates (NHPs), such as rhesus monkeys (Macaca mulatta) or common marmosets (Callithrix jacchus) inoculated with MERS-CoV via combined intratracheal, intranasal, oral, and ocular routes, develop transient respiratory disease with little or no viremia lethal disease was observed in a small number of marmosets [1,2,3,4]. 18F-Fluorodeoxyglucose ([18F]-FDG) PET/CT as a real-time noninvasive approach can be beneficial in providing biomarkers for host immune response and disease progression. [18F]-FDG-PET/CT has been used to track host immune response during monkeypox virus and human immunodeficiency virus-1 infections [5,6,7]
Experimental procedures were approved by the National Institute of Allergy and Infectious Diseases (NIAID), Division of Clinical Research (DCR), Animal Care and Use Committee and were in compliance with the Animal Welfare Act regulations, Public Health Service policy, and the Guide for the Care and Use of Laboratory Animals recommendations
Summary
The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. 18F-Fluorodeoxyglucose ([18F]-FDG)-positron emission tomography/computed tomography (PET/CT) as a longitudinal noninvasive approach can be beneficial in providing biomarkers for host immune response. [18F]-FDG uptake is increased in activated immune cells in response to virus entry and can be localized by PET imaging. The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, have not been fully characterized because a suitable animal model is currently not available. We used [18F]-FDG-PET/CT to investigate the host response developing in nonhuman primates after MERS-CoV exposure and applied kinetic modeling to monitor the influx rate constant (Ki) in responsive lymphoid tissue. The pathogenesis and immune response to Middle East respiratory syndrome (MERS) caused by a recently discovered coronavirus, MERS-CoV, has not been fully characterized, in part, because a suitable animal model that mimics human MERS is currently not available. 18F-Fluorodeoxyglucose ([18F]-FDG) PET/CT as a real-time noninvasive approach can be beneficial in providing biomarkers for host immune response and disease progression. We assessed the net [18F]-FDG uptake rate constant (Ki) in primary lymphoid tissues engaged in the host response to MERS-CoV exposure. This study is the first application of the methodology to an acute infectious disease process
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