Charlotte Busienne: understanding the encapsidation of HIV RNA
Charlotte Bussienne is a doctoral student at the IGBMC and works on the encapsidation of human immunodeficiency virus (HIV) RNA. In her research project, presented during the Alsace final of Ma Thèse en 180 Seconds, one of the objectives is to understand the role of the Gag protein in the recruitment of viral RNA. This step is crucial for the virus to become infectious and to spread in the body of infected persons. The doctoral student's goal is to propose a model for studying this step, in order to eventually find a molecule that would prevent viral replication.
HIV, a virus with a unique functioning
According to UNAIDS, the Joint United Nations Program on HIV/AIDS, 37.7 million people were living with HIV worldwide in 2020. This uniquely functioning virus poses many challenges to the scientific community, which is working to understand its mechanisms with the aim of providing different treatments to counter it.
HIV is the only human virus capable of integrating its genome, or "its construction instructions" as Charlotte Bussienne explained during her presentation, into the cell's DNA. Once integrated, both the virus and the cell's instructions are copied. They are, then, used to produce the viral proteins. "A protein can be considered as a building block that can have different roles" adds the doctoral student.
A particular viral protein called Gag is able to recruit viral RNA. "This protein is the main piece of the viral particle meaning that at the right time many copies of this protein will interact with themselves to form a box around the viral RNA" this is called the assembly step. Once assembled, the virus is then able to leave the cell to spread.
Better understanding the Gag protein, an essential protein for infection
The main question that Charlotte Bussienne is asking in her research is: what makes viral RNA found in HIV virus particles and not other RNAs, such as those in the cell? To answer this question, she is trying to understand how the Gag protein interacts with the viral RNA.
To do this, the doctoral student tries to take an image of the Gag protein in the presence of the RNA. She uses the Glacios cryo-electron microscope at the IGBMC and takes several shots to observe the structure of the protein, in particular to determine the location of its interaction with the viral RNA. This is a task made "difficult by the very small size of the protein: 1 million times smaller than a grain of sand".
Identifying how this step works could provide a new approach for the search for new treatments. Having several ways to fight this virus is crucial, as it mutates very quickly within an individual and quickly becomes resistant to treatment. Developing new strategies would allow us to continue to slow down the transmission of the virus and improve the quality of life of HIV-positive patients.
Charlotte Bussienne, PhD student specialising in virology
Charlotte Bussienne has a master's degree in virology from the University of Strasbourg. In 2019, she starts her thesis in co-direction with Dr Serena Bernacchi's team at the IBMC and the Lamour-Ruff team at the IGBMC.
My thesis in 180 seconds Alsace is not the first challenge in which the doctoral student is involved. In fact, in June 2021 Charlotte Bussienne was one of the winners of the Mature your PhD challenge, organised by SATT Conectus.