Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Eur J Immunol. 2013 Sep;43(9):2361-72. doi: 10.1002/eji.201243257. Epub 2013 Jun 25.
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 (DCs) compared with that by free HIV-1, but this increased infection was not observed with CD4(+) T cells. 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. Blocking the C-type lectin receptor macrophage mannose receptor (MMR) inhibited infection of emigrating DCs but had no effect on CD4(+) T-cell infection. We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4(+) 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.
HIV-1 与宿主的初始相互作用发生在性交过程中的黏膜处。在宫颈黏膜中，HIV-1 既以游离状态也以调理状态的病毒颗粒形式存在，这可能会影响初始感染。我们使用宫颈外植体来研究 HIV-1 的传播、调理作用对感染性的影响，以及如何预防感染。补体调理增强了 HIV-1 对树突状细胞 (DC) 的感染，与游离 HIV-1 相比，但这种增强的感染并未在 CD4(+)T 细胞中观察到。阻断 α4-、β7-和 β1-整合素显著抑制了 DC 和 CD4(+)T 细胞的 HIV-1 感染。我们发现，当阻断 αM/β2-和 α4-整合素时，与游离病毒颗粒相比，调理的病毒颗粒对 DC 中 HIV-1 感染的损害更大。阻断 C 型凝集素受体巨噬细胞甘露糖受体 (MMR) 抑制了迁移 DC 的感染，但对 CD4(+)T 细胞的感染没有影响。我们表明，阻断整合素可降低黏膜 DC 和从宫颈组织中迁移的 CD4(+)T 细胞的 HIV-1 感染。这些发现可能为新型杀微生物策略提供基础，这些策略可能有助于限制或预防宫颈黏膜的初始感染，从而减少或避免全身 HIV-1 感染。
