The human immune system secretes an endogenous protein that can strongly suppress coronaviruses, such as Sars-Cov-2, the pathogen that is responsible for causing the current Covid-19 pandemic.
Stephanie Pfänder is looking for genes that inhibit corona viruses. Image Credit: Ruhr-University Bochum, Marquard.
An international research team from Germany, Switzerland, and the United States effectively revealed that the LY6E protein inhibits coronaviruses from triggering an infection.
This finding might lead to the development of new therapeutic approaches against coronaviruses.”
Stephanie Pfänder, Study Lead Author and Professor, Department for Molecular and Medical Virology, Ruhr-Universität Bochum
The researchers published the study in the Nature Microbiology journal on July 23rd, 2020.
Strengthening influenza viruses, impairing corona viruses
The LY6E protein is involved in numerous diseases: Professor John Schoggins and Professor Charles Rice, both US researchers, identified that this protein improves the infectivity of influenza viruses. On the other hand, coronaviruses are suppressed by the LY6E protein.
During that time, Pfänder was working at the Institute of Virology and Immunology in Switzerland and visited Charles Rice’s laboratory at New York-based Rockefeller University in 2017, to detect genes that inhibit coronavirus infections. Pfänder was financially supported by a Marie Curie Individual Fellowship of the European Union.
Pfänder explained, “This led to the discovery that LY6E has the opposite effect on coronaviruses compared to influenza viruses.”
Additional analyses revealed that this inhibitory effect was exerted by the LY6E protein on all analyzed coronaviruses, such as the pathogens that cause Mers and Sars and also Sars-Cov-2, which is responsible for causing the Covid-19 infection.
Viruses unable to fuse
When the researchers tested different cell cultures, they observed that the LY6E protein impacts the potential of the virus to merge with the host cells.
If the virus is unable to fuse with these cells, it can’t cause infection.”
Volker Thiel, Study Corresponding Author and Professor, University of Bern
Verification in an animal model was effectively performed through an association with the John Schoggins’ laboratory at the Southwestern Medical Center of the University of Texas. The experiments performed at the laboratory revealed that the mouse variant of the protein, known as Ly6e, is important for protecting the immune cells against infections.
When the Ly6e protein is absent, immune cells, like B-cells and dendritic cells, become more vulnerable to infection, causing their numbers to reduce significantly. Mice that lack the Ly6e protein in their immune cells are highly vulnerable to a commonly non-lethal mouse coronavirus and eventually succumb to infection.
Understanding basic concepts
The scientists pointed out that the mouse coronavirus employed in the experiment varies considerably from the pathogen that is responsible for causing the current Covid-19 pandemic—for instance, it causes hepatitis instead of respiratory disease. Nonetheless, it is broadly accepted as a model for learning the fundamental ideas of immune responses and coronavirus replication in a living animal.
According to the study’s authors, “Our study provides new insights into how important these antiviral genes are for the control of viral infection and for an adequate immune response against the virus. Since LY6E is a naturally occurring human protein, we hope that this knowledge will aid the development of therapies that may one day be used to treat coronavirus infections.”
A therapeutic method that imitates the mode of action of the LY6E protein may offer a first line of defense against infections caused by the novel coronavirus.
Pfänder, S., et al. (2020) LY6E impairs coronavirus fusion and confers immune control of viral disease. Nature Microbiology. doi.org/10.1038/s41564-020-0769-y.