CCR5 or CXCR4 use influences the relationship between CD4 cell depletion, NKp44L expression and NK cytotoxicity in SHIV-infected macaques.

Abstract

OBJECTIVE:

HIV-1 infection is characterized by a progressive decline of CD4 cell count, the underlying mechanisms of which are still debated. We recently found that during HIV-1 infection, CD4 T cells overexpress a ligand of the NK activating receptor NKp44 (NKp44L) and are sensitized to NK cytolytic activity. The expression of NKp44L is triggered by a highly conserved motif of gp41 (3S) and is inhibited by anti-3S antibodies.

DESIGN:

To assess whether viral tropism can affect NKp44L expression, NK cytotoxicity, and anti-3S antibodies production, 10 macaques were infected either with the CCR5 tropic SHIV162P3 or with a CXCR4/CCR5 dual-tropic SHIV89.6P.

RESULTS:

In SHIV162P3-infected macaques, expression of NKp44L was inversely correlated with anti-3S antibodies, in relation to CD4 depletion and NK cytotoxicity. By contrast, no such correlation was found in macaques infected with SHIV89.6P which, induced a rapid decline of CD4 T cells.

CONCLUSIONS:

These results highlight the key role played by NK cells in CD4 cell count decline with respect to coreceptor usage, and provided the setting to investigate new strategies for preventive and/or therapeutic immunization to stimulate anti-3S antibodies.

• Authors: Vincent Vieillard, Raphaelle El Habib, Patricia Brochard, Benoit Delache, Hugues Fausther Bovendo, Julien Calvo, Julie Morin, Isabelle Picq, Frédéric Martinon, Bruno Vaslin, Roger Le Grand, Patrice Debré
• Journal: AIDS (London, England) (AIDS) Vol. 22 Issue 2 Pg. 185-92 (Jan 11 2008) ISSN: 1473-5571 [Electronic] England
• PMID: 18097220 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• HIV Envelope Protein gp41
• NCR2 protein, human
• Natural Cytotoxicity Triggering Receptor 2
• Receptors, CCR4
• Receptors, CCR5
• Receptors, CXCR4
• Receptors, Immunologic
• gp41 protein, Human immunodeficiency virus 1

Topics

• Amino Acid Motifs (immunology)
• Animals
• Antibodies, Viral (blood)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cytotoxicity Tests, Immunologic
• HIV Envelope Protein gp41 (chemistry, immunology)
• Killer Cells, Natural (immunology)
• Macaca fascicularis
• Natural Cytotoxicity Triggering Receptor 2
• Reassortant Viruses
• Receptors, CCR4
• Receptors, CCR5 (immunology)
• Receptors, CXCR4 (immunology)
• Receptors, Immunologic (immunology, metabolism)
• Simian Acquired Immunodeficiency Syndrome (blood, immunology, virology)
• Simian Immunodeficiency Virus (genetics, immunology)