Home Medical Research New insights offered into cell-to-cell propagation of SARS-CoV-2

New insights offered into cell-to-cell propagation of SARS-CoV-2

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New insights offered into cell-to-cell propagation of SARSCoV2

New insights offered into cell-to-cell propagation of SARS-CoV-2

It is possible to diagnose many different forms of viral diseases through the use of morphological study of viruses, and it is also possible to compare novel viral species with preexisting viruses. Despite the global public health catastrophe created by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the virus’s morphology and ultrastructure are still not totally understood, according to a recent report.

New insights offered into cell-to-cell propagation of SARSCoV2

As this terrible virus continues to spread over the world and claim the lives of millions of people, it is critical that we gain a better understanding of the morphology and ultrastructure of SARS-CoV-2.

Electronic microscopy (EM), and specifically transmission electron microscopy (TEM), is a potent technique in the field of molecular biology, and it is becoming increasingly popular. It is necessary for pathologists to study the tissues of coronavirus disease 2019 (COVID-19) patients using TEM because it enables for the visualization of SARS-CoV-2, which aids in the rapid detection of this virus in the samples collected from these patients. Because most pathologists are unfamiliar with techniques for analyzing viral particles and subcellular structures, the “virus-like particles” detected in multiple organs of COVID-19 patients have not been identified. The application of these techniques has the potential to provide substantially more knowledge about the structure and function of viruses.

Using standard transmission electron microscopy (TEM) and electron tomography (ET), researchers studied the three-dimensional (3D) morphological structure of SARS-CoV-2 particles and reassembled the images. Their findings were published in the journal Medical Molecular Morphology (ET). As a result, they were able to gather further information about the viral ultrastructure and morphology.

 

Study design

Using Vero E6/TMPRSS2 cell cultures, the researchers were able to generate the SARS-CoV-2 isolate JPN/TY/WK-521. Those cells that were infected with SARS-CoV-2 were harvested and fixed from the cell cultures. They employed ultrathin sections of 100nm including SARS-CoV-2 particles for investigation by conventional TEM with ET, and the results were published in Science. The application of ET to examine the 3D morphology of viruses allows for the in situ monitoring of the behavior of virions in target biological tissues or infected cells, which is not possible with other methods.

Morphological findings

These images, as well as the 3D images obtained by TEM and the sliced sequential ET images, revealed viral particles with diameters ranging between 100nm and 120nm, and which had cores with a high electron density. These particles were designated as SARS-CoV-2 virions since they were exclusively discovered in the infected Vero E6/TMPRSS2 cells and not in the uninfected cells, leading to the designation. They were found in vacuoles (big circular vesicles) and on the cell membrane surfaces, and they all looked to have the same morphological structure. Also visible in these images was the budding of the nucleocapsid in the membranes of vacuolar nuclei that included structural proteins, resulting in the formation of circular viral particles.

This research demonstrates that the morphology of SARS-CoV-2 particles in the vacuoles of infected cells is the same as the morphology of viral particles on the cell surface, and that both of these particles are fully mature viral particles. It was discovered that budding occurs exclusively within the vacuoles and not on the cell surface, and that immature virus particles were only found within the vacuoles and not on the cell surface.

These findings, taken combined, contribute to a better understanding of the cell-to-cell transmission of SARS-CoV-2 within the host. After the fusion of SARS-CoV-2 virus-containing vacuoles with the membrane of an infected host cell, mature viral particles are released from the infected cell and infect additional cells, which is the beginning of the infection cycle.

Conclusion

The study results reveal fresh insights on the cell-to-cell transmission and propagation of the SARS-CoV-2 virus, which was previously unknown. These findings may aid in the development of anti-SARS-CoV-2 prophylactic medicines that would restrict viral release from vacuoles and so help to prevent infection.

SARS-CoV-2 infection is a complex process, and the researchers provide a precise ET approach that will specifically aid researchers in their efforts to comprehend the end-to-end infection cycle of SARS-CoV-2, as well as the mechanisms of adhesion and infection of SARS-CoV-2 virions. The study also confirms that TEM and ET are the most effective in situ techniques for seeing virions detected in the tissues of virus-infected patients when compared to all other techniques. It is possible to display how SARS-CoV-2 replicates outside of the respiratory system using such a visualization technique.

The information revealed by the study in the form of 3D morphological images further confirms prior results that SARS-CoV-2 particles blossoming inside the vacuoles of host cells are morphologically identical to SARS-CoV-2 particles found outside of cells. The fact that both of these particles are mature viral particles means that they have the ability to infect other cells.

Specifically, this is the first report of its sort on the application of ET-generated reconstructed 3D pictures of the morphological structure of SARS-CoV-2 particles to plastic-embedded specimens, which was performed in this investigation. This new knowledge provides important new insights into the viral structure as well as the high-electron-density structure of the nucleocapsid in virions, both of which are currently unknown. This could be useful in the future when reexamining the morphologies of the viral specimens gathered during pathological sampling, for example.

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