When fossils come to life: SARS-CoV-2 spike, syncytin-1, and other curious fusion proteins

John Hewitt is a writer for Phys.org.

The spike glycoprotein from SARS-CoV-2 is a fusion protein. It can create multifarious syncytia among different cell types. The spike can perform these feats via multiple mechanisms acting at both the inside and outside of the cell.

Our syncytin-1 endogenous retroviral ENV protein and the GP160 ENV glycoprotein are examples of similar fusion functions. There are two different pre- and post-fusion configurations for GP160, which can be processed at its own furin cleavage site. The E is a small ENV protein that assembles into a presumptive cation channel with a central fusion pore.

There are no pro genes defined as such for the SARS-CoV-2 genome and the retroviruses, which must integrate into our DNA as part of their lifecycle. Researchers have found that the spike protein of the SARS-CoV-2 is involved in the activation of retroviruses in our cells, which contributes to observed pathology. What is going on here?

In light of some of the similarities, it has been suggested that the spikeProtein could potentially cross react in any tissues that express the retroviruses. During pregnancy, placental trophoblasts express a lot of useful HERVs such as ERVW1 (syncytin-1), ERVFRD-1 (syncytin-2), ERVV-1, ERVH48-1, ERVMER34 The degree of severity of some placental pathology is correlated with the expression of syncytin-2.

Researchers found that there is little chance of cross reactivity between spike and syncytin-1. Korean researchers wrote in the journal Animal Cells and Systems that there is no risk of cross reactivity or infertility because ancient genomic relics like HERVs can be activated in various tissues.

How can we better define this seemingly random activity, and what might we do about it, if spike protein is still capable of causing undesirable cell fusion? The terminology of cell fusion may be the first step. The author of the journal Oncotarget offers some food for thought. A syncytium produced from cells of the same type, for example, as in the fusion of two or more pneumocytes, is called a Homokaryon. A syncytium would be made from a pneumocyte fused to an epithelial progenitor. Whether cells can later sort themselves and their nucleus to generate competent mononuclear offspring is still unknown.

There are many forms of spike-induced syncytia in the lungs of COVID-10 patients, each with their own properties that can contribute to disease sequelae. ciliated cells in the airway, alveolar type 2 pneumocytes, and epithelial progenitors have all been found to participate in the oft-observed multinucleated and giant cells. A syncytium in the cells lining our blood vessels could contribute to thrombosis. A large area of the basement is exposed when a patch of fused cells is torn off. The main component of the basement is a 20-micron fiber of collagen.

Enough of this fear-mongering. The drugs that prevent spike-induced cell fusion and inhibit TMEM16F are already approved. TMEM16F is a calcium-activated ion channel that regulates the release of chloride from the cell surface, as well as a lipid scramblase that moves phosphatidylserine to the cell surface. This PS externalization is required for cell fusion. scram blases control the rate-limiting steps of the blood coagulation cascade.

The blood coagulation pathways are separate from the worms, but the main cause of blood coagulation is the scuplture of Factor X. The complexes are assembled on externalized PS. The downstream target factor FVIIa is unable to be activated until it is de-encrypted.

The realization that some fusogenic viral, or even retroviral proteins, which are fortuitously expressed in particular regions of the body may contribute to thrombotic events is of tremendous practical importance. Moderna has an extensive proposed line up of therapeutic amenities based on these proteins for all manner of viral insults to have some pause for inspection. There are many methods used to build antigenic spike proteins for vaccinations. Depending on how much of the spike code is used, which parts of the spike code are included, and which parts are not, very different proteins can be made. It is likely that full-length spikes in large questionable particles have been largely de-emphasized in favor of smaller but more immunogenic concoctions.

Lungs and blood vessels are critical areas of concern in any outbreak of the disease, but what about our precious neurons? It is clear that it can connect neurons in brain organoids, but what can researchers do with these instant research publication miracles? The fusion of neurons, glial cells, and even axons seems to be a common cause of neurological issues. The pseudorabies virus can cause axons to be fused to scythes. After the acute phase of herpes zoster, glia and fusions have been linked with long-term neuropathic pain. As of this Wednesday, we all know that the SARS-CoV-2 can use the vimentin as a way to attack cells. The prime marker used for identifying glial cells is vimentin.

Cell fusion may also be involved in this kind of pathology, as the rapidly expanding body of work looking at endogenous retroviruses re-activation in neurodegenerative disease further suggests.

More information: Serpen Durnaoglu et al, Syncytin, envelope protein of human endogenous retrovirus (HERV): no longer 'fossil' in human genome, Animal Cells and Systems (2022). DOI: 10.1080/19768354.2021.2019109 Journal information: Oncotarget

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Citation: When fossils come to life: SARS-CoV-2 spike, syncytin-1, and other curious fusion proteins (2022, January 27) retrieved 27 January 2022 from https://phys.org/news/2022-01-fossils-life-sars-cov-spike-syncytin-.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.