Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, USA.
Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA.
mSphere. 2018 Dec 12;3(6):e00540-18. doi: 10.1128/mSphere.00540-18.
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 passages, and were functional. Further evaluation indicated variable stability, but resolution limits hampered functional evaluation. These data support the further development of hNIS for monitoring infection in animal models of viral disease. 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.
单光子发射计算机断层扫描(SPECT)常用于肿瘤学和心脏病学领域,以评估疾病进展和/或治疗效果。该技术可实时评估疾病进展,应用于研究传染病时,可深入了解发病机制。将 SPECT 兼容的报告基因插入病毒中,可能有助于了解发病机制和病毒嗜性。人类钠碘转运体(hNIS)是一种 SPECT 和正电子发射断层扫描报告基因,将其插入中东呼吸综合征冠状病毒(MERS-CoV)中,该病毒是一种新出现的病毒,可导致人类严重的呼吸道疾病和死亡,从而获得病毒复制的定量和敏感标志物,以进一步开发 MERS-CoV 动物模型。评估了重组病毒的适应性、稳定性和报告基因功能。在峰值滴度和复制动力学方面,重组病毒和亲本病毒具有相同的适应性,稳定期可达 6 代,且具有功能。进一步评估表明其稳定性存在差异,但分辨率限制阻碍了功能评估。这些数据支持进一步开发 hNIS 用于监测病毒疾病动物模型中的感染。高级医学成像,如单光子发射计算机断层扫描与计算机断层扫描(SPECT/CT),增强了肿瘤学和心脏病学等领域。将 SPECT/CT、磁共振成像和正电子发射断层扫描应用于传染病可能会增强发病机制研究,并提供疾病进展的替代生物标志物。本文所述实验专注于将 SPECT/CT 兼容的报告基因插入 MERS-CoV 中,以证明可以将功能性 SPECT/CT 报告基因插入病毒中。