Regulation of Retroviral Infections


  HEADProf. BARRÉ-SINOUSSI Françoise / fbarre@pasteur.fr
  MEMBERSARNOLD Vincent / Dr BERGAMASCHI Anna / DAVID Annie / Dr KUNKEL Désirée
MARLIN Romain / Dr MENU Elisabeth / Dr MULLER-TRUTWIN Michaela
NUGEYRE Marie-Thérèse / Dr PANCINO Gianfranco / Dr ROSS Anna-Laura
Dr SAEZ-CIRION Asier / Dr SCOTT-ALGARA Daniel / Dr SHIN So Youn


  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:

- the resistance of CD4+ T lymphocytes from HIV-1 highly Exposed Non Infected individuals (ENI) implies constitutive mechanisms affecting either HIV-1 entry (low CCR5 co-receptor expression associated with heterozygous CCR5 mutations or elevated sensitivity to β-chemokines) or post-entry steps of replication of HIV-1 and of other retroviruses.

- the engagement of activating FcγR on macrophage surface suppresses lentiviral replication (HIV-1 as well HIV-2, SIVmac and SIVagm) by reducing viral reverse transcript levels and integration.

- the restriction of viral replication in placental trophoblast cells is affecting HIV-1 as well as other primate lentiviruses, can be partially overcome by a high dose of virus and implies, at least, viral env determinants.

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

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

- HIV-specific CD8+ T cells from HIV-1-infected individuals who remain with undetectable viremia in the absence of therapy (HIV controllers) exhibit a unique activation phenotype (CD38-HLA DR+) and are capable to suppress HIV infection in vitro by eliminating infected CD4+ T cells.

- non-pathogenic SIV infection in African Green Monkeys (AGM) correlates with a very rapid control of harmful T cell activation associated with a significant increase of plasmacytoid dendritic cells (pDC) in lymphoid tissues together with heightened levels of IFNα, of anti-inflammatory responses (TGFβ-1, IL10) and of markers of T regulatory cells like FoxP3.

- elevated levels of TNFαare contributing to an increasing risk of HIV-1 transmission at the materno-fetal interface, according to data on the reduction of placental TNFαby preventive antiviral therapy (AZT) and on the increased HIV-1 replication related to TNFαinduction by a Plasmodium falciparum antigen in placental cells.

- Natural Killer (NK) cell activation observed constitutively in HIV-1 highly Exposed Non Infected individuals (ENI) or in response to infected dendritic cells (DCs) might contribute respectively to a protective or harmful immune response to HIV-1.



  Publications

Publications 2006 of the unit on Pasteur's references database




Activity Reports 2006 - Institut Pasteur
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