Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin
Sensitivity of transmitted and founder human immunodeficiency virus type 1 envelopes to carbohydrate-binding agents griffithsin, cyanovirin-N and Galanthus nivalis agglutinin
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传播的和创始人人类免疫缺陷病毒 1 型包膜对碳水化合物结合剂 griffithsin、cyanovirin-N 和雪花莲凝集素的敏感性
DOI：
10.1099/jgv.0.000299
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发表时间：
2015-12-01
影响因子：
3.8
通讯作者：
Hu, Qinxue
中科院分区：
文献类型：
--
作者：
Hu, Bodan;Du, Tao;Hu, Qinxue
人类免疫缺陷病毒1型（HIV-1）的传播通常是由单一的传播/创始（T/F）病毒感染引起的。在这里，我们研究了T/F HIV-1包膜糖蛋白（Envs）对杀微生物剂候选碳水化合物结合剂（CBAs）griffithsin（GRFT）、氰威菌素-N（CV-N）和雪花莲凝集素（GNA）的敏感性，显示T/F Envs对CBAs表现出不同的敏感性，GRFT的IC 50值范围为0.006 +/- 0.0003至> 10 nM，CV-N为0.6 +/- 0.2至28.9 +/- 2.9 nM，GNA为1.3 +/- 0.2至> 500 nM。我们进一步揭示了在295或448位的去糖基化降低了T/F Env对GRFT的敏感性，并且在339位降低了对CV-N和GNA的敏感性。所有三种聚糖的突变使得CBA敏感的T/F Env对GRFT具有很大的抗性，表明T/F Env对GRFT的敏感性主要由295、339和448处的聚糖决定。我们的研究确定了与CBA敏感性相关的特异性T/F Env残基。
Human immunodeficiency virus type 1 (HIV-1) transmission often results from infection by a single transmitted/founder (T/F) virus. Here, we investigated the sensitivity of T/F HIV-1 envelope glycoproteins (Envs) to microbicide candidate carbohydrate-binding agents (CBAs) griffithsin (GRFT), cyanovirin-N (CV-N) and Galanthus nivalis agglutinin (GNA), showing that T/F Envs demonstrated different sensitivity to CBAs, with IC50 values ranging from 0.006 +/- 0.0003 to > 10 nM for GRFT, from 0.6 +/- 0.2 to 28.9 +/- 2.9 nM for CV-N and from 1.3 +/- 0.2 to > 500 nM for GNA. We further revealed that deglycosylation at position 295 or 448 decreased the sensitivity of T/F Env to GRFT, and at 339 to both CV-N and GNA. Mutation of all the three glcyans rendered a CBA-sensitive T/F Env largely resistant to GRFT, indicating that the sensitivity of T/F Env to GRFT is mainly determined by glycans at 295, 339 and 448. Our study identified specific T/F Env residues associated with CBA sensitivity.