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: We investigated the infection in DCs and CD4+ T cells after blocking CD4 with the mAb b12, a neutralizing antibody that specifically targets the CD4 binding site on gp120, and CCR5 with the inhibitor TAK779. We mostly used the b12 experiment to establish the level of inhibition reached in this model by a known blocker of HIV-1 infection 24. b12 significantly decreased the infection of migrating DCs to 45% of unblocked control for F-HIV (p = 0.019) and to 62% of control for C-HIV (p = 0.028) (Fig. 3A). When b12 was used, infection of CD4+ T cells emigrating from cervical explants was decreased by 85% (p < 0.0001) for F-HIV and by 74% (p < 0.0001) for C-HIV (Fig. 3B). The CCR5 inhibitor TAK799 decreased the HIV-1 infection of emigrating DCs by 41% (p = 0.037) for F-HIV and 66% for C-HIV (p = 0.06) and of CD4+ T cells by 48% (p = 0.02) for F-HIV and 68% (p = 0.01) for C-HIV (Fig. 3C and D).
Affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.