CCR5-reactive antibodies in seronegative partners of HIV-seropositive individuals down-modulate surface CCR5 in vivo and neutralize the infectivity of R5 strains of HIV-1 in vitro

Citation
L. Lopalco et al., CCR5-reactive antibodies in seronegative partners of HIV-seropositive individuals down-modulate surface CCR5 in vivo and neutralize the infectivity of R5 strains of HIV-1 in vitro, J IMMUNOL, 164(6), 2000, pp. 3426-3433
Citations number
45
Categorie Soggetti
Immunology
Journal title
JOURNAL OF IMMUNOLOGY
ISSN journal
00221767 → ACNP
Volume
164
Issue
6
Year of publication
2000
Pages
3426 - 3433
Database
ISI
SICI code
0022-1767(20000315)164:6<3426:CAISPO>2.0.ZU;2-J
Abstract
Exposure to HIV does not necessarily results in infection. Because primary HN infection is associated with CCR5-tropic HIV variants (R5), CCR5-specifi c Abs in the sera of HIV-seronegative, HIV-exposed individuals (ESN) might be associated with protection against infection. We analyzed sera from ESN, their HIV-infected sexual partners (HIV+), and healthy controls (USN) sear ching for CCR5-specific Abs,studying whether incubation of PBMC with sera c ould prevent macrophage inflammatory protein Ip (Mip1 beta ) (natural ligan d of CCR5) binding to CCR5, Results showed that Mip1 beta binding to CCR5 w as not modified by sera of either 40 HIV+ or 45 USN but was greatly reduced by sera of 6/48 ESN, Binding inhibition was due to Abs reactive with CCR5, The CCR5-specific Abs neutralized the infectivity of primary HIV isolates obtained from the corresponding HIV+ partners and of R5-primary HIV strains , but not that of CXCR4-tropic or amphitropic HIV strains.. Immunoadsorptio n on CCR5-transfected, but not on CXCR4-transfected, cells removed CCR5-spe cific and virus-neutralizing Abs, Epitope mapping on purified CCR5-specific Abs showed that these Abs recognize a conformational epitope in the first cysteine loop of CCR5 (aa 89-102), Affinity-purified anti-CCR5-peptide neut ralized the infectivity of R5 strains of HIV-1. Anti-CCR5 Abs inhibited Mip 1 beta-induced chemotaxis of PBMC from healthy donors. PBMC from two ESN (w ith anti-CCR5 Abs) were CCR5-negative and could not be stimulated by Mip1 b eta in chemotaxis assays. These results contribute to clarifying the phenom enon of immunologic resistance to HIV and may have implications for the dev elopment of a protective vaccine.