CCR5 or CXCR4 use influences the relationship between CD4 cell depletion, NKp44L expression and NK cytotoxicity in SHIV-infected macaques
| Autor: | Benoit Delache, Roger Le Grand, Frédéric Martinon, Hugues Fausther Bovendo, Vincent Vieillard, Julie Morin, Bruno Vaslin, Julien Calvo, Patrice Debré, Isabelle Picq, Patricia Brochard, Raphaelle El Habib |
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| Rok vydání: | 2008 |
| Předmět: |
CD4-Positive T-Lymphocytes
Receptors CXCR4 Receptors CCR4 Receptors CCR5 viruses Amino Acid Motifs Immunology Simian Acquired Immunodeficiency Syndrome Biology Antibodies Viral medicine.disease_cause CXCR4 Natural killer cell medicine Animals Immunology and Allergy Receptors Immunologic Cytotoxicity Tropism Natural Cytotoxicity Triggering Receptor 2 virus diseases Simian immunodeficiency virus Cytotoxicity Tests Immunologic Virology HIV Envelope Protein gp41 CD4 Lymphocyte Count Killer Cells Natural Macaca fascicularis Cytolysis Infectious Diseases medicine.anatomical_structure Tissue tropism biology.protein Simian Immunodeficiency Virus Antibody Reassortant Viruses |
| Zdroj: | AIDS. 22:185-192 |
| ISSN: | 0269-9370 |
| DOI: | 10.1097/qad.0b013e3282f35551 |
| Popis: | 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 SHIV 162P3 or with a CXCR4/CCR5 dual-tropic SHIV 89.6 P. Results: In SHlV 162P3 -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 SHIV 89.6p 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. |
| Databáze: | OpenAIRE |
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