Study of the Covid-19 virus: from the patient to the laboratory
Virologists have been closely involved in the battle against Covid-19, especially those from the Bordeaux campus. Read on for an interview with Marie-Édith Lafon and Harald Wodrich, co-leaders of the Spacvir team at the Fundamental Microbiology and Pathogenicity (MFP) laboratory.
"I remember the 22nd January 2020 very well. It was the day we had our first Covid-19 patient in Bordeaux", says Marie-Édith Lafon, professor at the University of Bordeaux, hospital practitioner and head of the Virology Department at Bordeaux University Hospital. Conducting her research at the Laboratory of Fundamental Microbiology and Pathogenicity (MFP – CNRS and University of Bordeaux), she shares the management of the Spacvir* team with Harald Wodrich, INSERM research director in virology. "Both on the hospital side and on the fundamental research side, our work suddenly changed."
Within the Spacvir team, researchers have been working for years on adenoviruses, respiratory viruses that mainly affect children. The body develops lifelong immunity after infection and the virus is no longer dangerous. However, adenoviruses can cause serious infections in patients undergoing immunosuppressivetherapy for organ transplants. "I raise questions while observing my patients and my colleagues study them with a fundamental approach," says Marie-Édith Lafon.
From adenoviruses to coronaviruses
How do adenoviruses infect cells? Why do they cause such an immune response? How does antiviral autophagy work, the process of cellular degradation that is also a response of the cell to stress in case of infection? What happens to the viral genome? To study these questions, MFP researchers have developed state-of-the-art imaging tools. "We are currently the only laboratory that can film viral replication or individual viral genomes in cells," explains Harald Wodrich. We know what is going on, where and when."
They were able to apply this technology to fight against another type of virus: the SARS-CoV-2 coronavirus. "When we decided to work on the Covid-19 virus, I had to get up to speed in 48 hours of non-stop reading," jokes Harald Wodrich. Scientists had to adapt their tools quickly and are now producing images of the viral processes, as part of the Anaconda project.
Funded by the ANR Flash Covid-19 call, the project aims to track infection in a differentiated bronchial epithelium model and assess the inflammatory response. The work is being carried out in collaboration with other teams and researchers from MFP (Marie-Line Andréola's team), the Bordeaux Imaging Center (BIC) platform, and the Bordeaux Cardio-Thoracic Research Center (CRCTB – INSERM and University of Bordeaux, Xavier Arnozan Hospital) with Thomas Trian. "We were among the first people to see SARS-CoV-2," recalls the virologist. We observe how its proteins behave in infected cells, how they move over time, which cells are infected..."
On the front line against SARS-CoV-2
During that time, Marie-Édith Lafon and her team at the Bordeaux University Hospital were on the front line, setting everything up on the clinical side. "Changing procedures and safety instructions, developing diagnoses with the PCR test... Everything had to be created from scratch." A new laboratory at Saint-André Hospital in Bordeaux was also opened to test the population on a large scale once the lockdown was over. "The number of annual tests exploded, we had to adapt to manage this wave," she says. "Marie-Édith is far too modest, if we have tests and the surveillance of the virus is still working in the south-west of France, it is largely because of the team she coordinates at the CHU, which continues to work tirelessly!" adds Harald Wodrich.
In recent months, the Spacvir team has also been conducting research with colleagues in Germany on the next generation of antivirals to target particle morphogenesis, the "packaging" of the viral genome. "The difficulty with variants is that we may find an inhibitor that stops an interaction between protein and receptor, but as soon as the virus mutates, this inhibitor might lose its effectiveness," says the scientist. So we are looking for processes that are better conserved in the virus, that is, specific interactions that must always be the same for the virus to survive, regardless of the variant." By tackling these interactions, the researchers hope the inhibitors will work even when the virus mutates can be developed.
"The good news this year is that two completely new types of vaccines have come out: messenger RNA vaccines such as the Pfizer-Biontech and Moderna vaccines, and the AstraZeneca and Janssen vaccines based on the "non-replicating viral vector" technique based on...adenovirus," says Marie-Édith Lafon. "These are very stable viruses and very good adjuvants, which is necessary to be a good vaccine vector," says Harald Wodrich. So we go back to our initial questions: how is the expression of an adenoviral vector regulated in a cell? Why are adenoviruses immunogenic?"
A potential revolution in vaccinology
On the clinical side, it is now important to know if and for how long vaccinated individuals will be immunized, especially for immunocompromised individuals. "I think this pandemic will completely change vaccinology, including for other viruses. I am convinced that flu vaccines will change, as will many others," concludes the virologist. "The potential of these advances is enormous."
Many projects on Covid-19
The team of Marie-Édith Lafon and Harald Wodrich is also involved in a second ANR project with Marie-Line Andréola and Andreas Bikfalvi, professor at the University of Bordeaux at the Laboratory of Angiogenesis and Microenvironment of Cancers (LAMC – Inserm and University of Bordeaux) in which they are seeking to understand how coronaviruses infect the cells of blood vessels. They are also working with Dr Guilhem Solé, head of the Reference Centre for Neuromuscular Diseases at the Bordeaux University Hospital, as part of a project funded by the French Association against Myopathies (AFM) to characterize the response to the Covid-19 vaccine in a group of patients with neuromuscular diseases.