Effect of lysine to arginine mutagenesis in the V3 loop of HIV-1 gp120 on viral entry efficiency and neutralization.
Effect of lysine to arginine mutagenesis in the V3 loop of HIV-1 gp120 on viral entry efficiency and neutralization.
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DOI：
10.1371/journal.pone.0119879
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Schreiber M
中科院分区：
文献类型：
--
作者：
Schwalbe B;Schreiber M
HIV-1感染的特征是持续复制，导致T淋巴细胞减少，这是由CCR 5向CXCR 4辅助受体使用的转换引起的。为了预测辅助受体的使用，已经开发了几种使用gp 120 V3环序列数据的计算机算法。在这些算法中，氨基酸赖氨酸（K）或精氨酸（R）之一对V3位置11和25的占据是CXCR 4使用的指标。氨基酸R和K在这两个位置占优势，但也可以在位置9和10处鉴定。通常，CXCR 4病毒具有V3序列，其总正电荷高于R5病毒的V3序列。通过从带正电荷的氨基酸（K和R）的数量中减去带负电荷的氨基酸（D，天冬氨酸和E，谷氨酸）的数量来计算净电荷。与极性和酸性性质非常相似的D和E相反，R胍基的特征与K铵基显著不同。然而，在辅助受体预测计算机算法中，R和K都是同等评级的。进行该研究以分析由于V3位置9、10和11处的R至K突变而导致的感染性和辅助受体使用的差异。构建了具有所有可能的RRR-KKK三联体的V3环突变体，并分析了辅助受体的使用、感染性和SDF-1α和RANTES的中和作用。病毒突变体R9 R10 R11表现出最高的感染率，并且与K9 K10 K11病毒相比更有效地被抑制。它们在病毒-gp 120配对感染测定中也显示出更高的效率。特别是V3环位置9与当被R占据时向更高感染性的转换相关。因此，K-to-R交换对增强病毒进入效率起作用，因此在基于V3序列数据预测病毒表型时应予以考虑。
HIV-1 infection is characterized by an ongoing replication leading to T-lymphocyte decline which is paralleled by the switch from CCR5 to CXCR4 coreceptor usage. To predict coreceptor usage, several computer algorithms using gp120 V3 loop sequence data have been developed. In these algorithms an occupation of the V3 positions 11 and 25, by one of the amino acids lysine (K) or arginine (R), is an indicator for CXCR4 usage. Amino acids R and K dominate at these two positions, but can also be identified at positions 9 and 10. Generally, CXCR4-viruses possess V3 sequences, with an overall positive charge higher than the V3 sequences of R5-viruses. The net charge is calculated by subtracting the number of negatively charged amino acids (D, aspartic acid and E, glutamic acid) from the number of positively charged ones (K and R). In contrast to D and E, which are very similar in their polar and acidic properties, the characteristics of the R guanidinium group differ significantly from the K ammonium group. However, in coreceptor predictive computer algorithms R and K are both equally rated. The study was conducted to analyze differences in infectivity and coreceptor usage because of R-to-K mutations at the V3 positions 9, 10 and 11. V3 loop mutants with all possible RRR-to-KKK triplets were constructed and analyzed for coreceptor usage, infectivity and neutralization by SDF-1α and RANTES. Virus mutants R9R10R11 showed the highest infectivity rates, and were inhibited more efficiently in contrast to the K9K10K11 viruses. They also showed higher efficiency in a virus-gp120 paired infection assay. Especially V3 loop position 9 was relevant for a switch to higher infectivity when occupied by R. Thus, K-to-R exchanges play a role for enhanced viral entry efficiency and should therefore be considered when the viral phenotype is predicted based on V3 sequence data.
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影响因子：
1.5
作者：
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通讯作者：
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影响因子：
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DOI：
10.1073/pnas.0404998101
发表时间：
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影响因子：
11.1
作者：
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影响因子：
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