National Institute for Communicable Diseases, Johannesburg, South Africa.
Virology. 2012 Feb 20;423(2):175-86. doi: 10.1016/j.virol.2011.12.001. Epub 2011 Dec 29.
It is generally believed that during the sexual transmission of HIV-1, the glycan-specific DC-SIGN receptor binds the virus and mediates its transfer to CD4(+) cells. The lectins griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN) inhibit HIV-1 infection by binding to mannose-rich glycans on gp120. We measured the ability of these lectins to inhibit both the HIV-1 binding to DC-SIGN and the DC-SIGN-mediated HIV-1 infection of CD4(+) cells. While GRFT, CV-N and SVN were moderately inhibitory to DC-SIGN binding, they potently inhibited DC-SIGN-transfer of HIV-1. The introduction of the 234 glycosylation site abolished HIV-1 sensitivity to lectin inhibition of binding to DC-SIGN and virus transfer to susceptible cells. However, the addition of the 295 glycosylation site increased the inhibition of transfer. Our data suggest that GRFT, CV-N and SVN can block two important stages of the sexual transmission of HIV-1, DC-SIGN binding and transfer, supporting their further development as microbicides.
普遍认为，HIV-1 的性传播过程中，糖基特异性的 DC-SIGN 受体与病毒结合，并介导其向 CD4+细胞转移。凝集素 griffithsin（GRFT）、氰钴胺素-N（CV-N）和 scytovirin（SVN）通过与 gp120 上富含甘露糖的聚糖结合来抑制 HIV-1 感染。我们测量了这些凝集素抑制 HIV-1 与 DC-SIGN 结合以及 DC-SIGN 介导的 CD4+细胞中 HIV-1 感染的能力。虽然 GRFT、CV-N 和 SVN 对 DC-SIGN 结合有一定的抑制作用，但它们强烈抑制了 DC-SIGN 介导的 HIV-1 转移。引入 234 个糖基化位点可消除 HIV-1 对凝集素抑制与 DC-SIGN 结合和病毒转移至易感细胞的敏感性。然而，添加 295 个糖基化位点会增加转移的抑制作用。我们的数据表明，GRFT、CV-N 和 SVN 可以阻断 HIV-1 性传播的两个重要阶段，即 DC-SIGN 结合和转移，支持它们作为杀微生物剂的进一步发展。
