Center for Molecular Medicine

HIV Research

The AIDS pandemic caused by the human immunodeficiency virus type 1 (HIV-1), with more than 30 million people infected worldwide, justifies a continued research effort. Molecular Medicine carries out strategic basic research in the field of molecular virology. We have specialized in viral nuclear import and integration in its cellular context. This research field overlaps with virology, cell biology, genetics and biochemistry. Creative research aims at identifying novel co-factors of HIV replication. Applications are in drug discovery and viral vector technology.

Standard therapy of infection with HIV-1 is based on potent cocktails of drugs targeting the viral protease and reverse transcriptase. An inhibitor of viral entry, enfuvirtide (T-20), has been added to these regimens. Inhibitors of the CCR5 coreceptor (maraviroc) and a strand transfer inhibitor of viral integrase have been recently approved for clinical use. Although this treatment has curtailed the number of AIDS deaths in western societies, these type of treatment regimens are often associated with severe and long term side effects and are almost unaffordable for the majority of patients living in sub-Saharan Africa. Moreover, incomplete suppression of HIV replication is associated with the emergence of drug-resistant HIV strains. The effort to make Highly Active Antiretroviral Therapy (HAART) available to low income countries is praised, but may increase the risk of antiviral resistance due to less than optimal settings of clinical follow up. Therefore, a continued research effort is required to develop more potent, cheaper and less toxic antiviral compounds to cope with rapidly emerging resistant strains and to offer a therapeutic perspective for patients living in developing countries.

HIV integrase

We have more than 10 years of experience in development of inhibitors targeting HIV integrase. Our drug discovery program encompasses (in collaboration) medicinal chemistry, drug design, structural biology, biochemistry, cell biology, virology, resistance development, preclinical evaluation. At present we mainly focus on:

• Molecular virology of resistance against strand transfer inhibitors
• Development of integrase inhibitors with alternative mechanisms of action

We welcome collaborations with academia and industry on this topic. We have a core facility for testing anti-integrase and anti-HIV compounds.

CONTACT:
If you are interested in this line of research please contact Dr. Frauke Christ. Frauke.christ@med.kuleuven.be

 

Cellular co-factors of HIV integrase

The insight has grown that HIV requires multiple cellular proteins to serve as co-factors for viral replication. HIV-1 has only a limited genetic make up, though it has to carry out multiple and distinct functions. Consequently, the virus takes advantage of cellular proteins and cellular pathways to complete the different steps in its life cycle. The conservation of these host factors is of advantage for designing therapeutic interventions. Our specific objective is to develop novel treatment strategies for HIV infection by targeting cellular co-factors required for HIV replication. Although antiviral drugs typically target viral proteins, we believe that a basic understanding of the interaction of specific cellular co-factors with HIV proteins, may finally result in specific drugs targeting these protein-protein interactions without cellular toxicity. The virus may find great difficulty in developing antiviral resistance against drugs targeting cellular proteins and conserved viral protein domains. Our group  identified and established intellectual property rights over the cellular protein, Lens Epithelium Derived Growth Factor (LEDGF/p75) as a crucial co-factor of HIV-1 integration. We have a pipeline of other potential co-factors of nuclear import and integration.

 

Figure 1. HIV relies on the interaction with multiple cellular proteins to complete its replication cycle. We focus on nuclear import and integration.

CONTACT:
If you are interested in this line of research please contact Dr. Zeger Debyser. Zeger.Debyser@med.kuleuven.be