Regulation of Retroviral Infections  


  HEADProfessor Françoise BARRE-SINOUSSI / francoise.barre-sinoussi@pasteur.fr
  MEMBERSARNOLD Vincent PhD student / BARRE-SINOUSSI Françoise PhD, Head of Unit / BERGAMASCHI Anna PhD, Post-doc / CANNOU Claude Technician, Laboratory assistant / CUMMINGS Jean Saville PhD, Post-doc / DAVID Annie PhD, Engineer / DELAIRE Marie-Claire Laboratory assistant (half time) / DIDIER Céline Senior Technician / HAMINI Chiraz Master2 / JACQUELIN Béatrice PhD, Engineer / JOULLIE Magali Executive Secretary / LIOVAT Anne-Sophie PhD student / MARLIN Romain PhD student
MENU Elisabeth PhD, Assistant Professor / MULLER-TRUTWIN Michaela PhD, Associate Professor / NUGEYRE Marie-Thérèse Engineer / PANCINO Gianfranco Md, PhD, Research Director / PETITJEAN Gaël PhD, Post-doc / ROSS Anna-Laura PhD, Post-doc / SAEZ-CIRION Asier PhD, Research assistant / SCOTT-ALGARA Daniel MD, PhD, Associate Professor
VERSMISSE Pierre Senior Technician / WEISS Laurence Professor, MD, phD, Université Paris V (20%)


  Annual Report

Unlike most other persistent viruses, HIV-1 progressively destroys the immune system, resulting in AIDS by very complex mechanisms that remain to be elucidated. Our laboratory is conducting research on the precise mechanisms underlying HIV/SIV pathogenesis and its control, specifically on cellular restriction mechanisms that may limit viral replication and on regulation by immune mechanisms, including critical components of the innate immunity, that may participate to harmful or favorable immune stimulation, using different models either in vitro or in human and non-human primates.

1-Regulation of viral replication by cellular restriction mechanisms.

Our investigations on host cells permissive or not to HIV-1 infection demonstrated that:

  • FcγR-mediated activation of monocyte-derived-macrophages inhibits HIV-1 reverse transcription and integration. The viral inhibition is associated with the induction of the CDK inhibitor p21Waf-1.

  • DCAF1 is a critical host effector of Vpx to mediate macrophage infection by HIV-2. Vpx assembly with the CUL4A-DDB1 ubiquitin ligase through DCAF1 recruitment may lead to the inactivation of an HIV-2 restriction factor in macrophages.

- trophoblast cells from the placenta recognise HIV-1 virions during the early steps of the viral life cycle and internalise them in an endocytic, receptor-independent manner, and either actively target HIV-1 for non-proteasomal degradation, or impede the release of the virions from the endosomes into the cytoplasm.

2- Regulation mediated by immune mechanisms, including components of the innate immunity.

Our recent investigations on both innate and adaptive immune regulations indicated that:

- CD8+T cells from HIV controllers (HICs) suppress ex vivoHIV-1 infection of autologous CD4+T cells, suggesting a crucial role of this response in the control of HIV replication in vivo. This anti-viral capacity correlates with the frequency of HIV-specific CD8+T cells, and in particular of Gag-specific response. However, some HICs have weak HIV-specific CD8+T cell responses, suggesting that other host mechanisms may contribute to control HIV infection in these patients.

- the control harmful T cell activation in the non-pathogenic SIV infection in African Green Monkeys (AGM) is the result of only moderate inflammatory responses during primary infection. The IFN-a production in vivoand the PDC homing to lymph nodes is weak and transient.

- antigen presenting cells from the decidua (uterine mucosa during pregnancy) are permissive in vitroto HIV-1 infection and this infection might be control by decidual NK cells at the materno-fetal interface to ensure natural protection against HIV-1 in uteromother-to-child transmission.

- CD85j positive Natural Killer (NK) cell subset is able to control HIV-1 replication in infected Dendritic cell and is mediated by cell to cell contact implicating the interaction between CD85j receptor and an unknown ligand distinct from HLA Class I molecules.

Keywords: HIV, SIV, Immune control, Innate Immunity, CD8+ T lymphocyte, natural killer cell, dendritic cell, macrophage, mother-to-child transmission, HIV controllers, immune activation, protection



  Publications

SCOTT-ALGARA D, ARNOLD V, DIDIER C,KATTAN T, PIROZZI G, BARRE-SINOUSSI F & PANCINO G. The CD85j+ NK cell subset potently controls HIV-1 replication in autologous dendritic cells. PLoS ONE. 2008;3:e1975.

Diop OM, Ploquin MJ, Mortara L, Faye A, Jacquelin B, Kunkel D, Lebon P, Butor C, Hosmalin A, Barré-Sinoussi F & Müller-Trutwin MC.Plasmacytoid dendritic cell dynamics and alpha interferon production during Simian immunodeficiency virus infection with a nonpathogenic outcome. J Virol. 2008 Jun;82(11):5145-52. Epub 2008 Apr 2.

Ahidjo Ayouba, Claude Cannou, Marie-Thérèse Nugeyre, Françoise Barré-Sinoussi, and Elisabeth Menu.Distinct efficacy of HIV-1 entry inhibitors to prevent cell-to-cell transfer of R5 and X4 viruses across a human placental trophoblast barrier in a reconstitution modelin vitro.Retrovirology. 2008; 5:31.

SAEZ-CIRION A, LACABARATZ C, LAMBOTTE O, VERSMISSE P, URRUTIA A, BOUFASSA F, BARRE-SINOUSSI F, DELFRAISSY JF, SINET M, PANCINO G & VENET A. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar CTL activation phenotype. Proc Natl Acad Sci USA 2007,104, 6776-6781

RAVET S, SCOTT-ALGARA D, BONNET E, TRAN HK, TRAN T, NGUYEN N, TRUONG XL, THEODOROU I, BARRE-SINOUSSI F, PANCINO G & PAUL P. Distinctive NK cell receptor repertoires sustain high-level constitutive NK cell activation in HIV-exposed uninfected individuals. Blood 2007, 109(10), 4296-305.



  Web Site

More informations on our web site




Activity Reports 2009 - Institut Pasteur
If you have problems with this Web page, please write to rescom@pasteur.fr