Viral Immunopathology - URA CNRS 3015  


  HEADYves Rivière / riviere@pasteur.fr
  MEMBERSF. Buseyne Assistant Professor / L. Durrieu Master 2, Paris 7 / O. Godon Master 2, Paris 7 / G. Janvier Technician / P. Louche Technician / Y. Rivière Associate Professor / J. Villeneuve Secretary


  Annual Report

The pediatric HIV infection differs from infection during adulthood by several points: i- in the mother-to-child transmission, the time of infection is well defined, mainly a few weeks before, and at delivery; ii- at the time of infection, the immune system of the child is partially immature, and has not been exposed to the pathogens responsible for opportunistic infections; iii- in the absence of antiretroviral treatment, the evolution of the disease is bimodal, as one-fifth of the children develop AIDS before one year of age while the remaining children evolve more slowly to the disease, like most infected adults; iv- during the first years of life, the plasma viremia is higher than in adults; v-children have higher thymic activity than adults, allowing a more efficient replenishment of destroyed CD4+T lymphocytes.

Our initial contribution was to show that CD8+CTL were present in a majority of infected children. Thus, perinatal exposure to HIV did not induce immune tolerance of T lymphocytes.Despite the relative immaturity of the immune system at time of infection, most HIV-infected children were able to mount an HIV-specific CTL response.Memory HIV-specific CTL response HIV-infected children was associated with a better clinical course, lower viral replication, and better viral reponse to treatment.Our data have added further support to the major role of functional HIV-specific CD8+T lymphocytes in controlling HIV replication. Importantly, our last data support that therapeutic vaccination expanding the HIV-specific CD8+T cell pool might be useful for young children with suppressed viremia, which have the lowest antiviral CD8+ (Buseyne et al., J.Inf. Dis., 2005).

HIV-DNA level in PBMC has recently been shown to be an independent predictor of disease progression. In PBMC, HIV-DNA is present as provirus and as well as unintegrated DNA in recently infected cells. Most studies report the absence of association between the frequency of HIV-specific IFN-γproducing CD8+T lymphocytes and plasma viral load. However, CD8+T lymphocytes recognize cell-associated viral peptides but not free virions. Therefore, we investigated whether any association could be found between HIV-DNA load in PBMC and the HIV-specific CD8+T lymphocytes frequency. The frequency of HIV-specific CD8+lymphocytes was directly correlated to age, inversely correlated to HIV-DNA independently of plasma HIV-RNA, CD4+and CD8+%. No correlation was observed between HIV-specific CD8+T lymphocytes and HIV-RNA, CD4+% or CD8+%. (Buseyne et al., Retrovirology, in press).

2- HCV-specific immune responses in HCV-uninfected individuals, collaboration with O. Launay and S. Pol, CIC and Hepatology Unit, Cochin hospital, M-L. Chaix and J-L. Bresson CHU Necker, D. Benomar EFS, Paris.

In a preliminary study we were able to detect a core-specific cellular immune response in a control group of volunteers not infected by HCV. The presence of a virus–specific T cell response in uninfected and presumably unexposed individuals could be due to an under-estimation of the frequency of a previous resolutive HCV infection, as most cases of acute HCV infection are clinically silent.An alternative not mutually exclusive hypothesis is the existence of a cross-reactivity between HCV antigens and other viral or common antigens present in the general population as reported previously by a few investigators. This result would modify our current concept of HCV prevalence. The goal of our current study was to estimate the presence of HCV-specific cellular immune responses in uninfected individuals without any known risk of a viral exposition (professional, nosocomial, familial, sexual) with a negative HCV PCR assay and humoral response by commercial assay.In 28 uninfected volunteers without any known risk of HCV exposition, HCV-specific circulating effector T lymphocytes responses have been studied using interferon g-Elispot and a CFSE proliferation assays from fresh PBMC. A panel of HCV-core-specific peptides was used for HCV-specific stimulation, and of SIV Gag or Nef-specific peptides as negative control. A core-specific T cell response was fully characterized with both assays (proliferation and gIFN-Elispot) in one out of the 28 volunteers tested. Part of this work has been submitted to the 43rd Annual Meeting of the European Association for the Study of the Liver, Milan, Italy, April 23-27, 2008[Rivière Y et al., HCV-Specific Immune Responses In Uninfected Individuals With No Known Risk For HCV Exposition].

Keywords: HIV-1, pediatric infection, T lymphocytes, HCV



  Publications

  1. Buseyne, F., Le Chenadec, J., Burgard, M., Bellal, N., Mayaux, MJ., Rouzioux, C., Rivière, Y. and S. Blanche. In HIV type 1-infected children cytotoxic T lymphocyte responses are associated with greater reduction of viremia under antiretroviral therapy.AIDS Res.Hum.Retroviruses. 21:719-27, 2005.

  1. Janvier, G., Chaix, ML., Fontaine, H., Bresson, JL., Pol, S., and Y. Riviere. The core-specific precursor T cell response is directed to the N-terminal and central parts of the protein and positively correlates to the viral load in chronically HCV-infected patients. Virology, 340:318-25, 2005.

  1. Buseyne, F., Scott-Algara, D., Bellal, N., Burgard, M., Rouzioux, C., Blanche, S. and Y. Riviere. The frequency of HIV-specific interferon-g-producing CD8 T cells is associated with both age and level of antigenic stimulation in HIV-1-infected children. J Infect Dis., 192:1781-6, 2005.

  1. Buseyne, F., Scott-Algara, D., Corre, B., Porrot, F., Monchatre, E., Bellal, N., Burgard, M., Rouzioux, C., Blanche, S. and Y.Rivière. Poor recognition of HIV-1 Nef protein by CD8 T cells from HIV-1-infected children: impact of age. Virology, 354 :271-279, 2006 .

  1. Buseyne, F., S. Blanche, M. Burgard, C. Milliancourt, D. Scott-Algara, C. Rouzioux, and R. Riviere, The frequency of HIV-specific CD8 T lymphocytes is inversely correlated to HIV DNA levels in untreated infected children Retrovirology, in press.





Activity Reports 2007 - Institut Pasteur
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