HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lopalco, L. Articles by Siccardi, A. G. Search for Related Content PubMed PubMed Citation Articles by Lopalco, L. Articles by Siccardi, A. G.

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 Vitro¹

Lucia Lopalco^2,*, Claudia Barassi^*, Claudia Pastori^*, Renato Longhi, Samuele E. Burastero^*, Giuseppe Tambussi^*, Francesco Mazzotta, Adriano Lazzarin^*, Mario Clerici^§ and Antonio G. Siccardi^¶

^* Department of Biological and Technological Research and Infectious Diseases Clinic, San Raffaele Scientific Institute, Milano, Italy; Istituto Biocatalisi e Riconoscimento Molecolare, Consiglio Nazionale delle Ricerche, Milano, Italy; Malattie Infettive, Ospedale S.M. Annunziata, Firenze, Italy; ^§ Cattedra di Immunologia, Università di Milano, Milano, Italy; and ^¶ Dipartimento di Biologia e Genetica per le Scienze Mediche, Milano, Italy

Exposure to HIV does not necessarily results in infection. Because primary HIV infection is associated with CCR5-tropic HIV variants (R5), CCR5-specific 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) searching for CCR5-specific Abs, studying whether incubation of PBMC with sera could prevent macrophage inflammatory protein 1ß (Mip1ß) (natural ligand of CCR5) binding to CCR5. Results showed that Mip1ß binding to CCR5 was 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. Immunoadsorption on CCR5-transfected, but not on CXCR4-transfected, cells removed CCR5-specific 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 neutralized the infectivity of R5 strains of HIV-1. Anti-CCR5 Abs inhibited Mip1ß-induced chemotaxis of PBMC from healthy donors. PBMC from two ESN (with anti-CCR5 Abs) were CCR5-negative and could not be stimulated by Mip1ß in chemotaxis assays. These results contribute to clarifying the phenomenon of immunologic resistance to HIV and may have implications for the development of a protective vaccine.