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Polyclonal Immunoglobulin G from Patients Neutralizes Human Immunodeficiency Virus Type 1 Primary Isolates by Binding Free Virions, but without Interfering with an Initial CD4-Independent Attachment of the Virus to Primary Blood Mononuclear Cells

Renaud Burrer, Sandrine Haessig-Einius, Anne-Marie Aubertin, and Christiane Moog^*

Inserm U544, Institut de Virologie, Université Louis Pasteur, 67000 Strasbourg, France

Received 14 November 2002/ Accepted 1 August 2003

We investigated the relationship between human immunodeficiency virus type 1 (HIV-1) primary isolate (PI) antibody-mediated neutralization and attachment to primary blood mononuclear cells (PBMC). Incubation of PIs with immunoglobulin G (IgG) purified from infected patients did not inhibit attachment of the viruses with PBMC, but partial to complete neutralization was achieved. Neutralization of PIs already fixed on the cells was achieved by some IgG samples only and was of limited intensity compared to the former neutralization protocol. On the contrary, the binding of IgG to free virions was shown to be sufficient to reach potent neutralization, as the infectivity of IgG-PI complexes purified from the bulk of antibodies before addition to PBMC was strongly diminished compared to mock-treated controls. Monoclonal antibodies to the CDR2 domain of CD4 completely inhibited the infection of PBMC without interfering with the attachment of PIs to the cells, suggesting that, under these experimental conditions, the initial attachment of viruses to PBMC involves alternative cellular receptors. This initial interaction may also involve other components of the viral envelope than gp120, as partial depletion of the surface glycoproteins of primary viral particles that resulted in an almost complete loss of infectivity did not impair attachment to PBMC. A limited inhibition of attachment was observed when interfering with putative interactions with cellular heparan sulfate, whereas no effect was observed for cellular CD147 or nucleolin or for virion-incorporated cyclophilin A. Altogether, our results favor a mechanism of neutralization of HIV-1 PIs by polyclonal IgG where antibodies predominantly bind free virions and neutralize without interfering with the attachment to PBMC, which, in this model, is mainly CD4 independent.

Present address: Neuropharmacology Department, The Scripps Research Institute, La Jolla, CA 92093.

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