Division of General Surgery, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Division of Immunology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Virology. 2021 Jan 15;553:1-8. doi: 10.1016/j.virol.2020.10.004. Epub 2020 Oct 26.
MUC5B and MUC7 salivary mucins are reported to inhibit HIV-1 entry into target cells in vitro; however, their relative inhibitory potencies have not been quantitively compared. There is also conflicting evidence regarding whether HIV-1 infection diminishes mucins' inhibitory efficacy. We explored the effect of donor HIV-1 status upon the anti-HIV-1 potency of purified MUC5B and MUC7 while comparing their relative inhibitory potential using a pseudovirus-based neutralization assay. HIV status of sample donors had no detectable effect on HIV-1 inhibition by salivary mucins. MUC5B (median IC 50 μg/ml, IQR 10-116 μg/ml) exhibited significantly more potent HIV-1 inhibition than MUC7 (median IC 458 μg/ml, IQR 192->2000 μg/ml; Mann-Whitney U p < 0.0001). We suggest that larger size, gel-forming properties and extensive glycosylation of MUC5B allow more effective binding and aggregation of viral particles. MUC5B is also more abundant in the saliva and is therefore likely to make a substantially greater contribution to it's anti-HIV-1 properties.
黏蛋白 MUC5B 和 MUC7 据报道可抑制 HIV-1 进入靶细胞,但其相对抑制效力尚未进行定量比较。此外,关于 HIV-1 感染是否降低黏蛋白抑制效果,也存在相互矛盾的证据。我们通过基于假病毒的中和测定,比较了纯化的 MUC5B 和 MUC7 的相对抑制潜力,同时探讨了供体 HIV-1 状态对其抗 HIV-1 效力的影响。样本供体的 HIV 状态对唾液黏蛋白抑制 HIV-1 没有明显影响。MUC5B(中位数 IC 50μg/ml,IQR 10-116μg/ml)比 MUC7(中位数 IC 458μg/ml,IQR 192->2000μg/ml;Mann-Whitney U p<0.0001)对 HIV-1 的抑制作用更强。我们推测 MUC5B 较大的分子量、凝胶形成特性和广泛的糖基化使其能够更有效地结合和聚集病毒颗粒。此外,MUC5B 在唾液中的含量也更高,因此可能对其抗 HIV-1 特性有更大的贡献。