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Blocking of integrins inhibits HIV ‐1 infection of human cervical mucosa immune cells with free and complement‐opsonized virions
Author(s) -
Tjomsland Veronica,
Ellegård Rada,
Kjölhede Preben,
Wodlin Ninni Borendal,
Hinkula Jorma,
Lifson Jeffrey D.,
Larsson Marie
Publication year - 2013
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201243257
Subject(s) - antibody opsonization , opsonin , biology , immune system , immunology , integrin , virology , infectivity , receptor , antibody , virus , biochemistry
The initial interaction between HIV ‐1 and the host occurs at the mucosa during sexual intercourse. In cervical mucosa, HIV ‐1 exists both as free and opsonized virions and this might influence initial infection. We used cervical explants to study HIV ‐1 transmission, the effects of opsonization on infectivity, and how infection can be prevented. Complement opsonization enhanced HIV ‐1 infection of dendritic cells ( DC s) compared with that by free HIV ‐1, but this increased infection was not observed with CD 4 + T cells. Blockage of the α4‐, β7‐, and β1‐integrins significantly inhibited HIV ‐1 infection of both DC s and CD 4 + T cells. We found a greater impairment of HIV ‐1 infection in DC s for complement‐opsonized virions compared with that of free virions when α M /β2‐ and α4‐integrins were blocked. Blocking the C ‐type lectin receptor macrophage mannose receptor (MMR) inhibited infection of emigrating DC s but had no effect on CD 4 + T ‐cell infection. We show that blocking of integrins decreases the HIV ‐1 infection of both mucosal DC s and CD 4 + T cells emigrating from the cervical tissues. These findings may provide the basis of novel microbicidal strategies that may help limit or prevent initial infection of the cervical mucosa, thereby reducing or averting systemic HIV ‐1 infection.

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