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


METHODS
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.
Vieillard
Vincent
V
INSERM U543, Laboratoire d'Immunologie Cellulaire et Tissulaire, Université Pierre et Marie Curie Paris-6, AP-HP, Paris, France. vincent.vieillard@chups.jussieu.fr
Habib
Raphaelle El
RE
Brochard
Patricia
P
Delache
Benoit
B
Bovendo
Hugues Fausther
HF
Calvo
Julien
J
Morin
Julie
J
Picq
Isabelle
I
Martinon
Frédéric
F
Vaslin
Bruno
B
Le Grand
Roger
R
Debré
Patrice
P
D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003601:Cytotoxicity Tests, Immunologic; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008252:Macaca fascicularis; D055629:Natural Cytotoxicity Triggering Receptor 2; D016865:Reassortant Viruses; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D015700:HIV Envelope Protein gp41; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; C514787:gp41 protein, Human immunodeficiency virus 1