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

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....

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Published in:	AIDS (London) Vol. 22; no. 2; pp. 185 - 192
Main Authors:	VIEILLARD, Vincent, EL HABIB, Raphaelle, LE GRAND, Roger, DEBRE, Patrice, BROCHARD, Patricia, DELACHE, Benoit, FAUSTHER BOVENDO, Hugues, CALVO, Julien, MORIN, Julie, PICQ, Isabelle, MARTINON, Frédéric, VASLIN, Bruno
Format:	Journal Article
Language:	English
Published:	Hagerstown, MD Lippincott Williams & Wilkins 11-01-2008
Subjects:	Amino Acid Motifs - immunology Animals Antibodies, Viral - blood Biological and medical sciences CD4 Lymphocyte Count CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cytotoxicity Tests, Immunologic HIV Envelope Protein gp41 - chemistry HIV Envelope Protein gp41 - immunology Human immunodeficiency virus 1 Human viral diseases Infectious diseases Killer Cells, Natural - immunology Macaca Macaca fascicularis Medical sciences Natural Cytotoxicity Triggering Receptor 2 Reassortant Viruses Receptors, CCR4 Receptors, CCR5 - immunology Receptors, CXCR4 - immunology Receptors, Immunologic - immunology Receptors, Immunologic - metabolism Simian Acquired Immunodeficiency Syndrome - blood Simian Acquired Immunodeficiency Syndrome - immunology Simian Acquired Immunodeficiency Syndrome - virology Simian Immunodeficiency Virus - genetics Simian Immunodeficiency Virus - immunology Viral diseases Viral diseases of the lymphoid tissue and the blood. Aids Tropism Ligand Cytotoxicity NKp44 ligand anti-3S gp41 antibody Immunological investigation T-Lymphocyte Primates CXCR4 chemokine receptor SHIV Antibody Retroviridae natural killer (NK) cells Lentivirus Virus Natural killer cell Infection CCR5 chemokine receptor CCR5 and CXCR4 viral tropisms Vertebrata Mammalia macaque model Models Simian immunodeficiency virus Chimera
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Summary:	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. 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. 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0269-9370 1473-5571
DOI:	10.1097/QAD.0b013e3282f35551