Natural antibodies to CCR5 from breast milk block infection of macrophages and dendritic cells with primary R5-tropic HIV-1.
In the present study, we demonstrate that breast milk of 66% and 83% of HIV-seronegative and seropositive women, respectively, contains natural Abs of the secretory IgA and IgG isotypes directed against the CCR5 coreceptor for R5-tropic strains of HIV-1. Abs to CCR5 were affinity purified on a matrix to which a synthetic peptide corresponding to the second extracellular loop of CCR5 had been coupled. The purified Abs bound to the CCR5 peptide in a dose-dependent fashion and to both native CCR5 expressed by Chinese hamster ovary cells transfected with CCR5 gene, macrophages, and immature dendritic cells. Although the avidity differed, the amount of anti-CCR5 Abs did not significantly differ between breast milk of HIV-seropositive and -seronegative women. Purified anti-CCR5 Abs inhibited up to 75% infection of macrophages and dendritic cells with HIV(BaL) and HIV(JR-CSF). Our observations provide evidence for a role of natural Abs to CCR5 in breast milk in controlling transmissibility of HIV through breastfeeding.
Bouhlal
Hicham
H
Institut Nationale de la Santé et de la Recherche Médicale (INSERM) U743, Equipe d'Immunité et Biothérapies Muqueuses et Université René Descartes Paris V, Institut Biomédical des Cordeliers, France. hicham.bouhlal@u430.bhdc.jussieu.fr
Latry
Vanessa
V
Requena
Mary
M
Aubry
Sylvie
S
Kaveri
Srinivas V
SV
Kazatchkine
Michel D
MD
Belec
Laurent
L
Hocini
Hakim
H
D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology; D019138:Antibodies, Blocking / Q000378:metabolism / Q000502:physiology*; D000915:Antibody Affinity; D001666:Binding Sites, Antibody; D065100:CCR5 Receptor Antagonists; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D008895:Milk, Human / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D019713:Receptors, CCR5 / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D019380:Anti-HIV Agents; D019138:Antibodies, Blocking; D065100:CCR5 Receptor Antagonists; D010446:Peptide Fragments; D019713:Receptors, CCR5