Viral infection : persistence, host response and pathophysiology

Coordinator : J. Izopet

Scientific Objectives


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).

Our projects


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.

Other details


Publications

2017

Lhomme, S; Bardiaux, L; Abravanel, F; Gallian, P; Kamar, N; Izopet, J

Hepatitis E Virus Infection in Solid Organ Transplant Recipients, France Journal Article

Emerg Infect Dis, 23 (2), pp. 353-356, 2017, ISSN: 1080-6059 (Electronic) 1080-6040 (Linking).

Links | BibTeX

2016

Abravanel, F; Barrague, H; Dorr, G; Saune, K; Peron, J M; Alric, L; Kamar, N; Izopet, J; Champagne, E

Conventional and innate lymphocytes response at the acute phase of HEV infection in transplanted patients Journal Article

J Infect, 72 (6), pp. 723-730, 2016, ISSN: 1532-2742 (Electronic) 0163-4453 (Linking).

Links | BibTeX

El Costa, H; Gouilly, J; Mansuy, J M; Chen, Q; Levy, C; Cartron, G; Veas, F; Al-Daccak, R; Izopet, J; Jabrane-Ferrat, N

ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy Journal Article

Sci Rep, 6 , pp. 35296, 2016, ISSN: 2045-2322 (Electronic) 2045-2322 (Linking).

Links | BibTeX

Gasser, R; Hamoudi, M; Pellicciotta, M; Zhou, Z; Visdeloup, C; Colin, P; Braibant, M; Lagane, B; Negroni, M

Buffering deleterious polymorphisms in highly constrained parts of HIV-1 envelope by flexible regions Journal Article

Retrovirology, 13 (1), pp. 50, 2016, ISSN: 1742-4690 (Electronic) 1742-4690 (Linking).

Links | BibTeX

Loiseau, C; Requena, M; Mavigner, M; Cazabat, M; Carrere, N; Suc, B; Barange, K; Alric, L; Marchou, B; Massip, P; Izopet, J; Delobel, P

CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals Journal Article

Mucosal Immunol, 9 (5), pp. 1137-50, 2016, ISSN: 1935-3456 (Electronic) 1933-0219 (Linking).

Links | BibTeX

Mansuy, J M; Dutertre, M; Mengelle, C; Fourcade, C; Marchou, B; Delobel, P; Izopet, J; Martin-Blondel, G

Zika virus: high infectious viral load in semen, a new sexually transmitted pathogen? Journal Article

Lancet Infect Dis, 16 (4), pp. 405, 2016, ISSN: 1474-4457 (Electronic) 1473-3099 (Linking).

Links | BibTeX

2015

Garcia-Perez, J; Staropoli, I; Azoulay, S; Heinrich, J T; Cascajero, A; Colin, P; Lortat-Jacob, H; Arenzana-Seisdedos, F; Alcami, J; Kellenberger, E; Lagane, B

A single-residue change in the HIV-1 V3 loop associated with maraviroc resistance impairs CCR5 binding affinity while increasing replicative capacity Journal Article

Retrovirology, 12 , pp. 50, 2015, ISSN: 1742-4690 (Electronic) 1742-4690 (Linking).

Links | BibTeX

Jeanne, N; Saliou, A; Carcenac, R; Lefebvre, C; Dubois, M; Cazabat, M; Nicot, F; Loiseau, C; Raymond, S; Izopet, J; Delobel, P

Position-specific automated processing of V3 env ultra-deep pyrosequencing data for predicting HIV-1 tropism Journal Article

Sci Rep, 5 , pp. 16944, 2015, ISSN: 2045-2322 (Electronic) 2045-2322 (Linking).

Links | BibTeX

Lhomme, S; Kamar, N; Nicot, F; Ducos, J; Bismuth, M; Garrigue, V; Petitjean-Lecherbonnier, J; Ollivier, I; Alessandri-Gradt, E; Goria, O; Barth, H; Perrin, P; Saune, K; Dubois, M; Carcenac, R; Lefebvre, C; Jeanne, N; Abravanel, F; Izopet, J

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy Journal Article

Antimicrob Agents Chemother, 60 (3), pp. 1608-14, 2015, ISSN: 1098-6596 (Electronic) 0066-4804 (Linking).

Links | BibTeX

2014

Kamar, N; Izopet, J; Tripon, S; Bismuth, M; Hillaire, S; Dumortier, J; Radenne, S; Coilly, A; Garrigue, V; D'Alteroche, L; Buchler, M; Couzi, L; Lebray, P; Dharancy, S; Minello, A; Hourmant, M; Roque-Afonso, A M; Abravanel, F; Pol, S; Rostaing, L; Mallet, V

Ribavirin for chronic hepatitis E virus infection in transplant recipients Journal Article

N Engl J Med, 370 (12), pp. 1111-20, 2014, ISSN: 1533-4406 (Electronic) 0028-4793 (Linking).

Links | BibTeX

Social impact

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.

Teaching commitment

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.

Alumni

Students :
H. Barragué TH
N. Capelli TH
Q. Chen TH
H. El Costa PDC
R. Gasser PDC
J. Gouilly TH
M. Nayrac TH

INSERM

INSERM

CNRS

CNRS

ANRS

ANRS

Sidaction

Sidaction

Hôpitaux de Toulouse

Hôpitaux de Toulouse

Agence de la biomédecine

Agence de la biomédecine