HIV latency. In patients, HIV infection can be controlled by combinatorial anti-retroviral therapy (cART). Interruption of treatment leads to viral rebounds within weeks and the therapy must therefore be continued for life, with the risk of secondary drug effects and emergence of resistant strains. Despite the current therapies, an HIV-1 cure is thus still highly desirable. The viral rebound is due to latently infected cells that provide the viral reservoir and that can be reactivated after even years of cART treatment. New strategies targeting the reservoir are essential for the development of a cure. Understanding the dynamics of the viral reservoir and how latent viruses are reactivated is thus essential to devise strategies that could eventually eradicate the virus.  Considering that i) the viral reservoir is maintained by clonal expansion of latently infected cells and ii) reactivation of latent cells is stochastic aand results from the transcriptional bursting of HIV-1 promoters, in collaboration with the team of Edouard Bertrand, we integrate HIV-1 transcription data into models describing the dynamics of latent cells in patients and to train these models with both experimental and clinical data. The resulting models will be used for further understanding of the viral rebound after treatment arrest and for testing cure strategies targeting the reservoir of latent cells.


  • K. Tantale, E. Garcia-Oliver, A. L’Hostis, Y. Yang, MC. Robert, T. Gostan, M. Basu, A. Kozulic-Pirhern, JC. Andrau, F. Muller, E. Basyuk*, O. Radulescu*, E. Bertrand*. Stochastic pausing at latent HIV-1 promoters generates transcriptional bursting. 2020, in revision Nature Communications. *corresponding authors. Bioarxiv doi:
Antigenic variation in malaria.

Var genes and chronic malaria. Most of the half-million annual deaths from malaria are caused by Plasmodium falciparum. This unicellular eukaryote parasite is transmitted by female Anopheles mosquitoes. After developing in the liver, thousands of merozoites (invasive single cells) are released and quickly invade red blood cells. Within the erythrocyte, the parasite divides mitotically and over a dozen new merozoites burst out of the red blood cell every 48 hours, increasing the parasitaemia exponentially. The heavy burden of clinical malaria is only the tip of the iceberg. The vast majority of all P. falciparum infections worldwide are characterized by low parasitaemia and the absence of clinical symptoms. This reservoir of chronic malaria represents a substantial challenge to malaria eradication strategies. During the intra-erythrocytic phase of the parasite life cycle, P. falciparum presumably escapes the immune system with antigenic variation, mediated at least in part by var genes. Each parasite genome contains about 60 different var genes. At the transcriptomic and proteomic level, var genes undergo mutually exclusive expression, i.e. at any given time only a single type of VAR protein is exposed at the surface of the infected red blood cell. Several authors developed models for antigenic variation that successfully explain clinical malaria data. However, these models predict that all the 60 var gene variants will appear in the first 10 generations, which is enough to protect the parasite against immunity during development of exponential parasitaemia, but cannot offer long-term protection during chronic infection. Recently, the team of Antoine Claessens in our lab showed that var genes undergo regular mitotic recombinations that generate novel “chimeric” sequences, and potentially encode new antigens. In collaboration with the team of Antoine Claessens, we are building mathematical models of antigenic variation with recombination that explain long-term parasitaemia.