Control mechanisms of virus replication in naturally SIVsmm infected mangabeys and experimentally infected macaques

F Villinger1, G T Brice, A Mayne

  • 1Winship Cancer, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. fvillin@emory.edu

Immunology Letters
|April 15, 1999
PubMed

Insights

Sooty mangabeys control SIV infection lifelong via CD8+ T-cells, unlike macaques. This study investigated chemokine pathways and T-cell function in SIV resistance, finding differences in T-cell function, not chemokines, explain disease resistance.

Area of Science:

  • Immunology
  • Virology
  • Primatology

Background:

  • Sooty mangabeys are naturally infected with SIV but do not develop disease, making them a valuable model for lentiviral infection studies.
  • Previous research indicated high frequencies of CD8+ T-cells inhibiting lentiviral replication in vitro via soluble factors in sooty mangabeys.
  • Understanding the role of beta-chemokines and their receptors in SIV resistance is crucial for identifying mechanisms of disease control.

Purpose of the Study:

  • To evaluate the potential contribution of beta-chemokines and their receptors in SIV-resistant sooty mangabeys compared to disease-susceptible macaques.
  • To investigate the ontogeny and maintenance of CD8+ T-cell-mediated inhibition of SIV replication in both species.

Main Methods:

  • Quantification of beta-chemokines (MIP-1alpha, MIP-1beta, RANTES) secreted by PBMC (peripheral blood mononuclear cells) from sooty mangabeys and macaques after in vitro stimulation.
  • Analysis of CCR-5 expression on T-cells and sequence analysis of key chemokine genes (MIP-1alpha, RANTES, MIP-1beta, CCR-5, CCR-2b, CXCR-4).
  • Assessment of the timing and persistence of CD8+ T-cell inhibitory function against SIV replication in relation to infection and disease progression.

Main Results:

  • Comparable levels of MIP-1alpha, MIP-1beta, and RANTES were secreted by both species' PBMC.
  • While constitutive CCR-5 expression was lower in mangabeys, T-cells from both species expressed CCR-5 after activation.
  • Sequence analyses revealed high homology for most chemokines and receptors between species and to human counterparts, except for MIP-1beta.
  • Crucially, sooty mangabeys acquired CD8+ T-cell inhibitory function long before seroconversion and maintained it lifelong, whereas macaques acquired it post-infection with subsequent loss.

Conclusions:

  • Differences in disease susceptibility between macaques and sooty mangabeys do not appear to be primarily due to variations in chemokine pathways.
  • The lifelong maintenance of CD8+ T-cell-mediated SIV inhibition in sooty mangabeys is a key factor in their natural resistance to lentiviral disease.
  • Rhesus macaque CD8+ T-cells possess the intrinsic potential to secrete inhibitory factors prior to SIV infection, suggesting regulatory mechanisms influence long-term control.

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