In a new study published in EMBO Journal on October 2, 2021, scientists from the Institut Pasteur, the CNRS, Université de Paris, the Vaccine Research Institute and Sorbonne University examined the fusion mechanisms of different SARS-CoV-2 variants: Alpha (initially identified in the United Kingdom), Beta (initially identified in South Africa) and Delta (initially identified in India). The Delta variant is now the dominant variant worldwide, and accounts for 99% of viral sequences in many countries.
Viral fusion is a mechanism that takes place at two moments in the viral replication cycle. The first stage starts when viral particles enter new host cells. The second stage occurs when the infected cell produces the spike protein at its surface and fuses with neighboring cells, forming giant cells known as syncytia.
These syncytia are found in the lungs of people with critical forms of COVID-19, but as yet little is known about their role. One hypothesis is that they could facilitate the spread of the virus or enable it to evade antibodies.
The main results of the study show that the Alpha, Beta and Delta variants form more syncytia in cell cultures than the ancestral strains of SARS-CoV-2. The Delta variant is the most "fusogenic," which may explain why this variant is more transmissible than the others.
The variants have different mutations on the spike protein. The scientists studied the role of each mutation and showed that the mutations could belong to one of three categories:
- Mutations that facilitate binding of the spike protein to the receptor (attaching the virus to the cell);
- Mutations that increase fusion (entry of the virus into the cell);
- Mutations that enable the virus to evade neutralizing antibodies.
Each variant has a specific combination of these mutations that improve viral propagation.
This study helps elucidate why some variants, especially the Delta variant, are more transmissible than the original strain of SARS-CoV-2 that caused the pandemic.
SARS-CoV-2 Alpha, Beta and Delta variants display enhanced Spike-mediated Syncytia Formation, EMBO Journal, October 2nd, 2021
Maaran Michael Rajah1,2, Mathieu Hubert1,3,#, Elodie Bishop1,4,#, Nell Saunders1,#, Remy Robinot1, Ludivine Grzelak1,2, Delphine Planas1,3, Jérémy Dufloo1,2, Stacy Gellenoncourt1,2, Alice Bongers1,2, Marija Zivaljic5,6, Cyril Planchais7, Florence Guivel-Benhassine1, Françoise Porrot1, Hugo Mouquet7, Lisa A Chakrabarti1 , Julian Buchrieser1* Olivier Schwartz1,2*.
1 Virus & Immunity Unit, Department of Virology, Institut Pasteur; CNRS UMR 3569, Paris, France
2 Université de Paris, Sorbonne Paris Cité, Paris, France
3 Vaccine Research Institute, Creteil, France
4 Sorbonne Université, Paris F-75005, France
5 Integrative Neurobiology of Cholinergic Systems, Department of Neuroscience, Institut Pasteur; CNRS UMR 3571, Paris, France
6 Sorbonne Université, ED3C “Brain, cognition, behavior”, Paris, France
7 Laboratory of Humoral Immunology, Department of Immunology, Institut Pasteur, INSERM U1222, Paris, France
# Second co-authors