AEGiS-15IAC: Chemokine/cytokine modulation by measles virus induces HIV-1 suppression in human lymphoid tissue ex vivo.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Chemokine/cytokine modulation by measles virus induces HIV-1 suppression in human lymphoid tissue ex vivo.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. TuOrA1185)

Grivel JC, Garcia M, Moss WJ, Margolis LB
NICHD/NIH, Bethesda, United States

BACKGROUND: Lymphoid tissues and organs are prominent sites of both measles virus and HIV-1 replication. HIV-infected children with acute measles were shown to have reduced plasma HIV-1 RNA levels. We tested the hypothesis that measles virus infection suppresses HIV-1 replication in lymphoid tissues.

METHODS: We infected human lymphoid tissues ex vivo with the R5 HIV isolate SF162 (R5[SF162]) or the X4 HIV isolate LAV.04 (X4[LAV.04]) alone or in combination with measles strains Chicago or Edmonstson. We evaluated viral replication and measured cytokines/chemokines in the culture medium of infected tissues.

RESULTS: Edmonston and Chicago measles virus strains efficiently replicate in lymphoid tissues ex vivo without exogenous stimulation. When co-infected with HIV-1, measles viruses dramatically suppress HIV-1 replication, especially of R5 phenotype. In co-infected tissues from 6 donors, replication of R5[SF162] was inhibited by 88±4% and replication of X4[LAV.04] was inhibited by 44±17%. Among 18 cytokines measured in culture medium from measles virus-infected lymphoid tissues, RANTES secretion was increased 2.5 fold (p<0.009).

CONCLUSIONS: Thus, measles virus suppresses HIV -1 replication in lymphoid tissues ex vivo likely by inducing the upregulation of RANTES, a strong R5 HIV-1 inhibitor, but inhibition of X4 HIV-1 suggests that other mechanism are also involved. The modulation of cytokine/chemokine networks by measles virus in human lymphoid tissue may represent a general mechanism of microbial interactions. Further understanding of measles virus-triggered upregulation of chemokines at the site of HIV-1 infection might result in development of new therapeutic approaches to HIV disease.

Keywords: AEGIS, HIV-1, Chemokines, HIV Infections, Measles virus, Virus Replication, HIV, Acquired Immunodeficiency Syndrome, Lymphoid Tissue, RANTES, Receptors, HIV, HIV Envelope Protein gp120, HIV Antibodies, Anti-HIV Agents, HIV Seropositivity, Chicago, Child, Humans, virology, immunology

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TuOrA1185