Team AMARA & MEERTENS

Biology and Pathogenesis of Viral Infections (VIRPATH)

The development of effective antiviral treatments is a major priority in the fight against emerging viral epidemics, a significant cause of morbidity and mortality worldwide, as illustrated by the COVID-19 pandemic. Most currently available antivirals target viral proteins, a strategy that promotes the emergence of resistance and often limits their spectrum of activity. In contrast, host-targeting antiviral approaches exploit the close dependence of viruses on cellular machinery. By targeting cellular factors essential for viral replication, these strategies offer the potential to reduce the risk of viral escape while paving the way for the development of broad-spectrum antivirals. Through large-scale genetic screens and mass spectrometry-based proteomics approaches, our team has identified numerous cellular proteins playing a key role in the infectious cycle of several emerging viruses, including dengue, Zika, Mayaro, respiratory syncytial virus, SARS-CoV-2, and Oropouche virus. We are now analyzing, at the molecular level, the mechanisms by which these viruses hijack these host factors, with the goal of identifying novel exploitable cellular vulnerabilities for the development of innovative antiviral strategies.

BK polyomavirus (BKPyV) is a ubiquitous DNA virus that establishes latent infection in the urinary tract in more than 90% of the population. In immunocompromised patients — particularly after kidney transplantation or hematopoietic stem cell transplantation — alterations in immune homeostasis promote BKPyV reactivation, which can lead to lytic infection of the epithelial cells of the urinary tract. This reactivation is responsible for severe complications, such as BKPyV-associated nephropathy and hemorrhagic cystitis. The marked increase in the use of transplantation, particularly kidney transplantation, has made BKPyV an emerging public health concern. This issue is all the more critical given that it remains difficult to identify patients at risk of complications, and no specific antiviral treatment is currently available, with management relying essentially on modulation of immunosuppression. Faced with this therapeutic impasse, our team has developed an integrated approach aimed at deciphering the molecular mechanisms of BKPyV infection. By combining the use of primary human cells, renal organoids, and clinical samples, we seek to map the virus-host interactions essential to the BKPyV infectious cycle, to elucidate the mechanisms controlling viral latency and its reactivation in the context of immunosuppression, and to characterize anti-BKPyV immune responses at both the systemic and tissue levels. This work aims to pave the way for the development of innovative antivirals targeting BKPyV, the identification of clinically exploitable diagnostic and prognostic biomarkers, and the establishment of relevant preclinical models for studying pathogenesis and evaluating new therapeutic strategies. This project is part of the FHU TRANSVIR (“Innovative strategies to treat chronic viral infections after hematopoietic stem cell and solid organ transplantation”), a structured program led by our team that brings together clinicians and researchers around persistent viral infections in transplant patients. It benefits in particular from close collaborations with the teams of Alexandre Loupy (Paris Institute for Transplantation & Organ Regeneration) and Sophie Saunier (Institut Imagine, Paris), as well as the biotech company Aircuris (https://www.aicuris.com/).