Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions.
Bottom Line: Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4(+) T cells.We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked.We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4(+) T cells emigrating from the cervical tissues.
Affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.Show MeSH
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Mentions: To study the impact of C-type lectins on infection in DCs and CD4+ T cells, we exposed cervical mucosa to the mannose polymer mannan, a competing ligand for C-type lectins, before challenging the tissues with HIV-1. Infection was decreased for both F-HIV (46%, p = 0.005) and C-HIV (40%, p = 0.023) in emigrating DCs after blocking C-type lectins located in the cervical mucosa (Fig. 4A). In contrast, no effect on the infection of emigrating CD4+ T cells was observed (Fig. 4B). DCs emigrating from cervical tissues have been shown to express MMR 24. Blocking this C-type lectin using anti-MMR mAb gave similar results as when C-type lectins were blocked using mannan with a 51% (p = 0.006) decrease in F-HIV infection in DCs (Fig. 4C). When the cervical tissue was challenged with C-HIV, the corresponding decrease in DC infection was 43% (p = 0.029) (Fig. 4C). As expected, infection of CD4+ T cells was not affected by blocking MMR in the cervical mucosa (Fig. 4D). Blocking of MMR had a slightly higher effect on DC infection with F-HIV than with C-HIV.
Affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.