Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN.

Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN.
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DOI:
10.1016/j.virol.2013.07.019
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发表时间:
2013-11
期刊:
影响因子:
3.7
通讯作者:
Morris, Lynn
Morris, Lynn
中科院分区:
医学3区
文献类型:
--
作者:
Alexandre, Kabamba B.;Moore, Penny L.;Nonyane, Molati;Gray, Elin S.;Ranchobe, Nthabeleng;Chakauya, Ereck;McMahon, James B.;O'Keefe, Barry R.;Chikwamba, Rachel;Morris, Lynn

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我们检测了HIV-1亚型C对抑制凝集素griffithsin (GRFT)、cyanovirin-N (CV-N)和scytovirin (SVN)产生耐药性的能力,这些凝集素在gp120上结合多种富含甘露糖的聚糖。在这些凝集素浓度不断升高的条件下培养的四株原代HIV-1菌株对其50%抑制浓度的耐受性增加了2至12倍。gp120的序列分析显示,大多数基因缺失1 ~ 5个富含甘露糖的聚糖。C2区230、234、241、289位点和C3-C4区339、392、448位点的糖基化位点受到影响。此外,4株分离株中有3株在V4区发现了多达5个氨基酸的缺失和插入。这些数据表明gp120上糖基化位点的缺失以及V4中聚糖的重排是HIV-1亚型C从GRFT、CV-N和SVN中逃逸的机制。
We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339, 392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN.
DOI: 10.1038/nri2569
发表时间: 2009-07
期刊: Nature reviews. Immunology
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