A signature in HIV-1 envelope leader peptide associated with transition from acute to chronic infection impacts envelope processing and infectivity.
A signature in HIV-1 envelope leader peptide associated with transition from acute to chronic infection impacts envelope processing and infectivity.
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DOI：
10.1371/journal.pone.0023673
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Letvin NL
中科院分区：
文献类型：
--
作者：
Asmal M;Hellmann I;Liu W;Keele BF;Perelson AS;Bhattacharya T;Gnanakaran S;Daniels M;Haynes BF;Korber BT;Hahn BH;Shaw GM;Letvin NL
人类免疫缺陷病毒（HIV）的粘液传播导致病毒遗传多样性的瓶颈。Gnanakaran及其同事使用一种计算策略来识别Envelope中特定位置的签名氨基酸，这些位置与感染早期采样的传输序列或慢性感染期间采样的序列相关。在观察到的最强的签名中，是在传播和早期感染时在位置12处组氨酸的稳定存在的富集，以及在慢性感染中在位置12处组氨酸的复发性损失。该氨基酸位于包膜的前导肽内，该蛋白质的一个区域已被证明影响包膜糖蛋白表达和病毒粒子感染性。我们显示了一个带正电荷的氨基酸之间的强关联，如组氨酸在位置12的传输/创始人病毒与更有效的运输新生包膜多肽的内质网和更高的稳态糖蛋白表达相比，病毒有一个非碱性的位置12的残基，一个取代，是丰富的病毒从慢性感染的个人。当在其他病毒蛋白的背景下表达时，具有碱性氨基酸位置12的传输包膜以更高的密度掺入病毒中，并且表现出比非特征包膜更高的感染性滴度。这些结果支持使用计算方法来检查大型病毒序列数据集的功能特征的潜在效用，并表明包膜表达水平对于有效的HIV传播的重要性。
Mucosal transmission of the human immunodeficiency virus (HIV) results in a bottleneck in viral genetic diversity. Gnanakaran and colleagues used a computational strategy to identify signature amino acids at particular positions in Envelope that were associated either with transmitted sequences sampled very early in infection, or sequences sampled during chronic infection. Among the strongest signatures observed was an enrichment for the stable presence of histidine at position 12 at transmission and in early infection, and a recurrent loss of histidine at position 12 in chronic infection. This amino acid lies within the leader peptide of Envelope, a region of the protein that has been shown to influence envelope glycoprotein expression and virion infectivity. We show a strong association between a positively charged amino acid like histidine at position 12 in transmitted/founder viruses with more efficient trafficking of the nascent envelope polypeptide to the endoplasmic reticulum and higher steady-state glycoprotein expression compared to viruses that have a non-basic position 12 residue, a substitution that was enriched among viruses sampled from chronically infected individuals. When expressed in the context of other viral proteins, transmitted envelopes with a basic amino acid position 12 were incorporated at higher density into the virus and exhibited higher infectious titers than did non-signature envelopes. These results support the potential utility of using a computational approach to examine large viral sequence data sets for functional signatures and indicate the importance of Envelope expression levels for efficient HIV transmission.
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影响因子：
3.7
作者：
LI, Y;LUO, LZ;KANG, CY
通讯作者：
KANG, CY
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
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影响因子：
5.4
作者：
Frater, A. J.;Edwards, C. T. T.;Fidler, S.
通讯作者：
Fidler, S.
影响因子：
5.4
作者：
Abrahams, M. -R.;Anderson, J. A.;Williamson, C.
通讯作者：
Williamson, C.
DOI：
10.1073/pnas.93.18.9606
发表时间：
1996-09-03
影响因子：
11.1
作者：
Li, Y;Bergeron, JJJM;Kang, CY
通讯作者：
Kang, CY