SARS-CoV-2 evades neutralizing antibodies and rapidly spreads by cell fusion, finds study

Once a virus infects a cell, neighboring cells are likely to become infected by interactions that are dependent on the cell and the virus in question. For example, cell-to-cell spread is facilitated in HIV by viral synapses, which also allow for escape from neutralizing antibodies. Low-level drug inhibitors are able to suppress infection if applied before the first cell is infected, but not after, demonstrating the lower sensitivity towards antiviral therapy-induced by this cell-to-cell transfer method.

Concerning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative pathogen of coronavirus disease 2019 (COVID-19) – cell-to-cell spread has been observed by a process of cell fusion, involving major changes in cytoskeleton regulation and expression of the spike protein on the cell surface, allowing interaction with neighbors. Syncytia, single cells containing several nuclei formed by cell fusion, are frequently seen in the lungs of COVID-19 patients, indicating this method of cell-to-cell spread.

In a new study by researchers in the UK, Germany and South Africa, this process is visualized using time-lapse microscopy of a human cell lung line, demonstrating that SARS-CoV-2 can induce cell-to-cell fusion within 6 hours post-infection. Further, the application of neutralizing monoclonal antibodies or convalescent plasma was unable to prevent the spread of the virus by this mechanism, suggesting that removing SARS-CoV-2 from cells permissive of cell membrane fusion could be more difficult than other types of cell.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

A preprint version of the study is available on the bioRxiv* server, while the article undergoes peer review.

How was the study performed?

The group began by engineering a human lung cell line capable of infection with SARS-CoV-2, with fluorescent nuclei that can be easily visualized by microscopy. In particular, an angiotensin-converting enzyme 2 (ACE2) receptor expressing H1299 non-small cell carcinoma line bearing yellow protein labeled histone tags was utilized, providing sufficient but non-overexpressed fluorescent tagging of the nucleus.

Upon introducing one such cell infected with SARS-CoV-2 to a culture of uninfected cells, the group observed syncytia formation, which did not occur in the absence of infection. Interestingly, the nuclei were seen to cluster into organized ring structures, and by 36 hours post-infection, around 20% of the nuclei had been drawn into such structures. Cells that had become infected underwent little cell division, evidenced by the minimally rising then falling number of nuclei in the culture induced by initial division of neighboring cells before the infection spreads.

To examine whether the ability of neutralizing antibodies to suppress the virus was dependent on the method of cell-to-cell spread, the authors utilized SARS-CoV-2 bearing the D614G mutation seen in the earliest variants of concern, such as the UK B.1.1.7 variant, which was compared with later lineages such as B.1.351 that have additional mutations to the spike protein: L18F, K417N, E484K, and N501Y. When applying convalescent plasma sourced from individuals that have recovered from the former, the latter frequently exhibits improved escape from neutralizing antibodies. This was confirmed by the group by in vitro infection studies, with the B.1.351 variant better avoiding capture by antibodies generated against B.1.1.7. However, the reverse was also true, with antibodies generated against B.1.351 being equally effective towards the earlier strain also. After concluding that these antibodies, both sourced from convalescent individuals or as monoclonal antibodies, could neutralize the cell-free virus, they were applied to infected H1299 cells as above. It was seen that they had little to no effect in suppressing cell-to-cell transmission.

Given the rapid cell-to-cell infection cycle observed here, it is little wonder why innate antibody responses, which take several weeks to fully develop, are rarely capable of effectively removing the virus once cells are infected. As vaccines provide ongoing neutralizing antibody circulation for a period of several months, they could better allow the removal of free virus before it enters cells and subsequently spreads while evading capture.

The group points out that their model utilized a lung cancer cell line modified to express ACE2, and therefore may not perfectly replicate real-world conditions. However, syncytia are a commonly observed feature in the lungs of COVID-19 patients, and cells heavily expressing the SARS-CoV-2 spike protein on the surface were used, which should therefore have been an effective target for neutralization, while none was observed. They suggest that future prevention and treatment strategies may need to more heavily consider the role of cell-to-cell transmission in SARS-CoV-2, which likely enhances the virulence and persistence of the virus.

This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources

Journal references:

Article Revisions

  • Apr 8 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
Michael Greenwood

Written by

Michael Greenwood

Michael graduated from the University of Salford with a Ph.D. in Biochemistry in 2023, and has keen research interests towards nanotechnology and its application to biological systems. Michael has written on a wide range of science communication and news topics within the life sciences and related fields since 2019, and engages extensively with current developments in journal publications.  

Citations

Please use one of the following formats to cite this article in your essay, paper or report:

  • APA

    Greenwood, Michael. (2023, April 08). SARS-CoV-2 evades neutralizing antibodies and rapidly spreads by cell fusion, finds study. News-Medical. Retrieved on October 15, 2024 from https://www.news-medical.net/news/20210604/SARS-CoV-2-evades-neutralizing-antibodies-and-rapidly-spreads-by-cell-fusion-finds-study.aspx.

  • MLA

    Greenwood, Michael. "SARS-CoV-2 evades neutralizing antibodies and rapidly spreads by cell fusion, finds study". News-Medical. 15 October 2024. <https://www.news-medical.net/news/20210604/SARS-CoV-2-evades-neutralizing-antibodies-and-rapidly-spreads-by-cell-fusion-finds-study.aspx>.

  • Chicago

    Greenwood, Michael. "SARS-CoV-2 evades neutralizing antibodies and rapidly spreads by cell fusion, finds study". News-Medical. https://www.news-medical.net/news/20210604/SARS-CoV-2-evades-neutralizing-antibodies-and-rapidly-spreads-by-cell-fusion-finds-study.aspx. (accessed October 15, 2024).

  • Harvard

    Greenwood, Michael. 2023. SARS-CoV-2 evades neutralizing antibodies and rapidly spreads by cell fusion, finds study. News-Medical, viewed 15 October 2024, https://www.news-medical.net/news/20210604/SARS-CoV-2-evades-neutralizing-antibodies-and-rapidly-spreads-by-cell-fusion-finds-study.aspx.

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Mild COVID-19 disrupts brain connectivity and reduces memory function in adolescents and young adults