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Characterizing Viral Infection by Electron Microscopy: Lessons from the Coronavirus Disease 2019 Pandemic
Shreeram Akilesh1, Roberto F Nicosia1, Charles E Alpers1
1Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Abstract:
The severe acute respiratory syndrome coronavirus 2 pandemic has infected millions of individuals in the United States and caused hundreds of thousands of deaths. Direct infection of extrapulmonary tissues has been postulated, and using sensitive techniques, viral RNA has been detected in multiple organs in the body, including the kidney. However, direct infection of tissues outside of the lung has been more challenging to demonstrate. This has been in part due to misinterpretation of electron microscopy studies. In this perspective, we will discuss what is known about coronavirus infection, some of the basic ultrastructural cell biology that has been confused for coronavirus infection of cells, and rigorous criteria that should be used when identifying pathogens by electron microscopy.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is found in kidneys, but direct infection of these organs is difficult to prove. This perspective clarifies electron microscopy criteria for identifying SARS-CoV-2 in extrapulmonary tissues.
Area of Science:
- Virology
- Pathology
- Microscopy
Background:
- The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to widespread illness and mortality.
- Viral RNA detection in extrapulmonary organs, including the kidney, suggests potential direct infection beyond the lungs.
- Demonstrating direct SARS-CoV-2 infection in tissues outside the lung has remained a challenge.
Purpose of the Study:
- To discuss current knowledge of coronavirus infection in extrapulmonary tissues.
- To differentiate true viral infection from artifactual cellular structures observed via electron microscopy.
- To establish rigorous criteria for identifying viral pathogens using electron microscopy.
Main Methods:
- Review of existing literature on SARS-CoV-2 infection and electron microscopy.
- Analysis of ultrastructural cell biology relevant to viral identification.
- Development of a framework for rigorous pathogen identification in tissues.
Main Results:
- Misinterpretation of electron microscopy findings has complicated the assessment of extrapulmonary SARS-CoV-2 infection.
- Basic cellular ultrastructure can be mistaken for viral particles.
- Clear, rigorous criteria are needed to confirm viral presence.
Conclusions:
- Accurate identification of SARS-CoV-2 in extrapulmonary tissues requires strict adherence to established electron microscopy criteria.
- Distinguishing viral infection from cellular artifacts is crucial for understanding the full scope of SARS-CoV-2 pathogenesis.
- Standardized methods will improve the reliability of research on viral dissemination.
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