Neutralizing monoclonal antibodies to human immunodeficiency virus type 1 do not inhibit viral transcytosis through mucosal epithelial cells.

Abstract:

:HIV-1 transcytosis has been proposed as a potential mechanism allowing the virus to cross the epithelium during mucosal transmission. Epitopes of the HIV-1 envelope involved in this process have not been identified yet. Here, we assessed a large panel of HIV neutralizing antibodies recognizing well-characterized epitopes of the HIV-1 envelope for their ability to block HIV-1 transcytosis across a confluent epithelial monolayer. We found that all of the 13 HIV-1-specific monoclonal antibodies tested in the present study, including the three broadly neutralizing antibodies 2F5, 2G12 and IgG1b12, lacked the ability to inhibit transcytosis of cell-free and cell-associated R5- as X4-tropic HIV-1 across a tight and polarized monolayer of HEC-1 epithelial cells. In contrast, anti-gp160 polyclonal antibodies purified from serum or breast milk of HIV-1-infected individuals potently inhibited HIV-1 transcytosis. Furthermore, polymeric S-IgA exhibited similar ability to inhibit transcytosis compared to IgG despite their lower anti-gp160 specific activity. Together, these results demonstrate that the major neutralizing envelope epitopes of HIV-1 are not involved in HIV-1 transcytosis, and suggest that surface agglutination of virus particles may participate to the blocking effect observed with both polyclonal and polymeric anti-gp160 immunoglobulins.

journal_name

Virology

journal_title

Virology

authors

Chomont N,Hocini H,Gody JC,Bouhlal H,Becquart P,Krief-Bouillet C,Kazatchkine M,Bélec L

doi

10.1016/j.virol.2007.09.006

subject

Has Abstract

pub_date

2008-01-20 00:00:00

pages

246-54

issue

2

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(07)00590-9

journal_volume

370

pub_type

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