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Recombinant human CD40 ligand inhibits simian immunodeficiency virus replication: a role for interleukin- 16

M E Lee1, S Z Bucur, T W Gillespie

  • 1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Journal of Medical Primatology
|December 11, 1999
PubMed

Insights

Recombinant human CD40 ligand (huCD40L) inhibits simian immunodeficiency virus (SIV) replication in vitro. This antiviral effect involves increased interleukin-16 (IL-16) mRNA expression and reduced viral antigen production.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • CD40 ligand (CD40L) on T cells interacts with CD40 on immune cells.
  • HIV infection diminishes CD4+ T cell CD40L expression.
  • An in vitro model using rhesus macaques with simian immunodeficiency virus (SIV) was employed.

Purpose of the Study:

  • To investigate the effect of recombinant human CD40L (huCD40L) on SIV replication in an in vitro model.
  • To explore the mechanisms underlying huCD40L's antiviral activity.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from SIV-infected rhesus macaques were cultured with huCD40L.
  • Viral p27 antigen production was measured.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to analyze SIV gag and IL-16 mRNA expression.

Main Results:

  • huCD40L induced PBMC proliferation independently of cytokines.
  • A 70% reduction in p27 production by SIV-infected PBMCs was observed (P < 0.05).
  • RT-PCR revealed decreased SIV gag mRNA and increased IL-16 mRNA expression.

Conclusions:

  • huCD40L inhibits SIVmac239 replication, including antigen and mRNA production.
  • The antiviral effect appears to be mediated by huCD40L-induced IL-16 mRNA expression.
  • This response is independent of beta-chemokines.

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