Viral infection : persistence, host response and pathophysiology
Coordinator : J. Izopet
Our team specializes in the pathophysiology of infections with human immunodeficiency virus (HIV), hepatitis E virus (HEV) and zika virus (ZIKV). The major specific topic is the mechanisms underlying the persistence of virus in immunocompetent hosts (HIV, ZIKV) and immunocompromised patients (HEV). We are also working on how HIV enters host cells via chemokine receptors and the pathophysiology of HIV infection in the intestinal mucosa. Another aspect of our work is the route of transmission and pathogenesis of HEV and ZIKV during pregnancy. We have developed a number of specific model cell systems, including placental explants, extravillous cytotrophoblasts, hepatocytes, enterocytes, peripheral and tissue lymphocytes, together with systems based on clinical samples (intestinal tissue, early and term placenta, blood and biopsies from immunocompromised patients).
AXIS 1: HIV
We are interested in the mechanisms underlying HIV entry into target cells and their impact on the pathogenesis of infection and the development of AIDS. We are contributing to the design and study of how entry inhibitors direct against HIV receptors (CD4, CCR5 or CXCR4) act and the way in which the virus resist/escape to the action of these inhibitors.
The immune restoration of the intestinal mucosa of patient on antiretroviral therapy is delayed and incomplete. We have shown that the chemiotaxis axis CCR9-CCL25 and CCR6-CCL20 is altered and are now determining the impact of these alteration on the populations of Th17, Th1, Treg and TCD8 lymphocytes.
AXIS 2: HEV
Other members of the team are characterizing the immune response to HEV (TCD4+, TCD8+, NK, T gamma-delta) in subjects such as immunocompromised hosts, pregnant women and the elderly, who frequently present with symptomatic infections.
This includes determining the genetic diversity of the virus and its impact on pathogenesis, particularly during pregnancy. We are interested in the virus life cycle, particularly how the virus leaves infected cells. We have already demonstrated that ribavirin has an antiviral effect on HEV and we are now investigating how the virus becomes resistant to this drug during the treatment of chronic hepatitis E.
AXIS 3: ZIKV
We are studying the replication of ZIKV in the genital compartment and at the maternofetal interface. We have evidence that ZIKV replicates differentially in a wide range of maternal and fetal cells, including decidual fibroblasts and macrophages, trophoblasts and umbilical cord mesenchymal stem cells.
Our latest results show that the virus persists in the semen of infected patients for a long time and that the spermatozoa bear viral antigens. We are now looking at the mechanisms the virus uses to persist in the genital compartment.
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Knowledge of the biology of RNA viruses and pathophysiological mechanisms.
Our research generates fundamental knowledge about chronic viral infections (HIV and HEV) and emerging infection (ZIKV), and clinical applications to combat these viruses whose pathophysiology remains unclear. Our links with the clinical departments of Toulouse University Hospital, with the technical platform of the CPTP and several international collaborations ensure the optimal development of original themes.
Our team members are committed to the teaching of students in the faculties of Medicine and Pharmacy; we also welcome Master and PhD students from both France and abroad to work and study in our laboratory.
H. Barragué TH
N. Capelli TH
Q. Chen TH
H. El Costa PDC
R. Gasser PDC
J. Gouilly TH
M. Nayrac TH