Our research group is pursuing a number of simultaneous objectives:
The first one is to better understand the resistance to antiretroviral drugs (ARV), although they significantly change the prognosis of the disease.
At present, HIV infection cannot be cured.
The AIDS Reference Laboratory (laboratoire de référence SIDA (LRS)) is active in monitoring the spread of drug resistance. In collaboration with others Belgian ARLs and Sciensano, our team has described a large cluster of transmission of an NRTI (non-nucleoside reverse transcriptase inhibitor) resistant strain and more recently an F1 subtype epidemic in men who have sex with men. The LRS of UCLouvain is part of the Belgian board of ESAR "European Society for Translational Antiviral Research" and collaborates in monitoring the spread of drug resistance in Europe. The recent widespread use of integrase inhibitors (INSTI) in the treatment of HIV-infected individuals has resulted in a surveillance program for potential resistance transmission. Jointly, the impact of natural genetic polymorphisms on the efficacy of ARVs is being studied in national and international collaborations. The laboratory is also involved in a project in rural South Africa initiated by the pediatricians of Cliniques Universitaires Saint-Luc. The prevalence of ARV resistance in infants infected with HIV at birth is being studied to establish better indications for their treatment.
The LRS is also trying to better understand the potential clinical impact of minority variants of HIV-1 through various projects conducted on a high-throughput sequencing platform or NGS (Next-Generation Sequencing).
Various projects aimed at cure require specific laboratory tools that are not yet available for clinical routine. We are focusing on the detection of residual viremia on treatment and its clinical impact through the validation of ultra-sensitive methods such as digital PCR.
Over the last few years, the LRS has become the reference for HIV-2 in Belgium and Luxembourg, both for research and for laboratory tests related to clinical follow-up. The laboratory coordinates clinical data for the international AcHIeV2e collaboration and participates in the development of genotypic interpretation rules for ARV resistance (HIV-2 EU).
The second objective is trying to improve cure strategies by focusing on cell restriction factors. The laboratory is currently focusing on an antiviral restriction factor that interferes with viral replication and in particular on the interaction between a viral envelope glycoprotein (gpTM) and the cellular protein BST-2 also called tetherin, interfering with virion release. Directed mutagenesis, viral replication and protein interaction studies are performed in the laboratory. In addition, our research aims to identify genetic variability within the bst-2 gene. Results should include patient history, viral load, and disease progression classification (controllers or not).
Our laboratory has also highlighted the role of the HIV-2 envelope glycoprotein in modulating antiviral responses of infected cells, including regulation of the NF-kB signaling pathway. We demonstrated that the HIV-2 envelope protein, like the HIV-1 envelope glycoprotein, was able to activate this cellular transcription factor. However, unlike HIV-1, HIV-2 does not seem to express an inhibitor protein of this transcription factor NF-kB, which is involved in the expression of hundreds of antiviral genes (cytokines, interferons, restriction factors, ...). The HIV-1 Vpu protein, antagonistic to tetherin, is a potent inhibitor of the NF-kB signaling pathway, whereas antagonism of tetherin by the HIV-2 envelope glycoprotein does not inhibit this signaling pathway. This results in a high expression of antiviral genes at the end of the viral cycle, which would hinder HIV-2 replication. These results support the fact that the host immune system controls HIV-2 more effectively than HIV-1.
thérine par la glycoprotéine d'enveloppe du VIH-2.
Our laboratory is also involved in a collaboration with the IRCM of the University of Montreal in a study that attempts to describe the immunoregulatory role of tetherin in the secretion of interferons by dendritic cells via the binding of tetherin to the dendritic cell receptor ILT7, in a context of antagonism of tetherin by the envelope glycoprotein of HIV-2.