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Worldwide there are more than 1 x 1031 viruses, which can potentially spread and result in outbreaks, such as the COVID-19 pandemic. It is hence important to study them and understand the way they replicate in order to prevent their spread. One common technique used to study viruses and their genome is transmission electron microscopy (TEM).
The SARS-CoV-2 virus is behind the current COVID-19 pandemic that has affected the whole world since the outbreak started in December 2019 in Wuhan, China. The virus has been spreading rapidly since, leading to many deaths and severe consequences on the economies of countries worldwide.
How to reduce the spread of a virus
There are two essential steps to reducing the spread of a virus: understanding how it replicates and finding effective ways to diagnose infections. Being able to explain in detail how the virus replicates is also key to understanding its contagiousness and modeling the ways and rates at which it can transmit.
Although lockdown measures and hygiene precautions have been found to be effective to reduce the spread of the virus, they do not offer a long-term solution to the problem. In the SARS-CoV-2 case, it is important to study the genome of the virus in order to fully understand why it causes severe respiratory problems and organ failures, as well as for discovering ways to diagnose and treat infections.
Methods to detect viral infections
Although pathologists have been using molecular methods to detect viral infections for decades, there are many limitations to these techniques. For example, in order to detect a virus using a molecular method, such as a PCR test, prior knowledge of its morphology as well as how and where within the cell it assembles is required.
Hence, the virus must first be studied using another technique in order to obtain this prior knowledge, which is essential for making the correct diagnosis. One method that has been used for years to discover and study viruses is TEM. TEM is a well-established technique that uses a beam of electrons that interact with the sample and are transmitted through it, generating a highly magnified image.
Suitability of TEM for virus detection
With its nanometre scale resolution, TEM is a suitable tool to study viruses, including the SARS-CoV-2 virus. One limitation posed by this technique, however, is that analysis and interpretation of results are very complex. Virologists and scientists with expertise in SARS-CoV-2 pathology have to work together alongside electron microscopists in order to fully develop the potential of this method for virus detection.
Although there are some viral diagnostics laboratories that use electron microscopy for virus detection, TEM is not usually used in routine settings for diagnosis. Requiring very specific expertise, it is a very expensive technology that is not available in most laboratories.
TEM is suitable for obtaining prior knowledge of the morphology of the virus for the identification of unknown infectious agents in particular outbreaks. It also allows the recognition of viruses from different families that have very different morphologies. Another important advantage of TEM is that it can be used to identify multiple infections caused by more than one virus.
This technique is hence suitable for detecting unexpected infectious agents which could be missed by molecular diagnostic methods. Moreover, the nature of the samples that can be analyzed could be diverse, ranging from body fluids analyzed directly to cell cultures, analyzed in vitro.
Combining TEM with molecular methods
The advantages of TEM make it a very suitable technique for virus detection but the disadvantages, associated with its cost and operation, pose a limitation on it as a routine diagnostic technique.
Studying a virus with TEM allows the identification of the viral structure in order to conclude what reagents have to be used for creating a routine diagnostic test. TEM and molecular diagnostic techniques are hence often complementary to each other. Additionally, TEM can be used to confirm the diagnosis established using a routine molecular technique, such as a PCR test.
Studying viruses to prevent pandemics
Detecting viruses, such as the SARS-COV-2 virus, and studying their structure and replication mechanisms, is crucial in developing methods for their diagnosis, treatment, and prevention, as well as identifying new strains and limiting their spread.
Having widely accessible and accurate tests is essential for slowing down the spread of the virus. In combination with vaccines, having access to methods such as TEM to study the way a virus behaves and evolves might be one of the keys to handling the COVID-19 pandemic and preventing future outbreaks.
References
Microbiology by numbers. Nat Rev Microbiol 9, 628 (2011). https://doi.org/10.1038/nrmicro2644
Morse, S. S. (1996). Emerging viruses. Oxford University Press on Demand.
Roingeard, P. et al., (2019) Virus detection by transmission electron microscopy: Still useful for diagnosis and a plus for biosafety. Reviews in Medical Virology. https://doi.org/10.1002/rmv.2019
Hopfer, H. et al., (2021) Hunting coronavirus by transmission electron microscopy – a guide to SARS-CoV-2-associatedultrastructural pathology in COVID-19 tissues. Histopathology. https://doi.org/10.1111/his.14264
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