Destroying the human immunodeficiency virus before infection
- Department / Centre
- Biochemistry and Pharmacology
- Bio21 Molecular Science and Biotechnology Institute
|A/Prof Isabelle Rouillerfirstname.lastname@example.org|
Summary The Rouiller group uses cryo-EM to determine the structures of medically important protein complexes. Lab members investigate how these proteins assemble into molecular machines and study how they function in the context of health and disease. We are particularly interested in proteins relevant for cancer treatment, antibiotic resistance, vaccine development and neurodegenerative diseases.
Despite numerous advances in treatment and prevention, 37 million people are currently infected with HIV worldwide. The difficulty in treating HIV is that the virus hides inside a subset of the host immune cells, the T-cells. The solution to this problem would be to destroy the virus before it is able to enter the T-cells using the antibody-dependent cellular cytotoxicity (ADCC) mechanism. This mechanism requires recognition of the virus by neutralizing antibodies. The HIV-1 envelope glycoprotein trimer (Env), the only viral protein on the surface of virion, is thereby the main target for neutralizing antibodies. The challenge is that, at the surface of the virus, Env adopts a compact, closed conformation that is largely antibody resistant. After binding to its receptor at the surface of T cells, Env undergoes conformational changes and becomes more vulnerable to ADCC. Non-neutralizing antibodies also increase the stability of this vulnerable conformation.
Our lab is characterising using cryo-EM the conformations adopted by Env in response to chemical mimicking the T cells receptor and to binding of non-neutralizing antibodies. The overarching aim of this project is to define and characterize at the molecular level the exact cocktail of antibodies and chemicals to use in order to induce a conformational change in Env so that is recognised and destroyed by the immune system. This knowledge would allow both treatment of HIV infection and the development of vaccines.