Virogenetics Laboratory of Virology, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
Microbiology Department, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387 Krakow, Poland.
Molecules. 2021 Jun 18;26(12):3732. doi: 10.3390/molecules26123732.
Mass spectrometry (MS) used in proteomic approaches is able to detect hundreds of proteins in a single assay. Although undeniable high analytical power of MS, data acquired sometimes lead to confusing results, especially during a search of very selective, unique interactions in complex biological matrices. Here, we would like to show an example of such confusing data, providing an extensive discussion on the observed phenomenon. Our investigations focus on the interaction between the Zika virus NS3 protease, which is essential for virus replication. This enzyme is known for helping to remodel the microenvironment of the infected cells. Several reports show that this protease can process cellular substrates and thereby modify cellular pathways that are important for the virus. Herein, we explored some of the targets of NS3, clearly shown by proteomic techniques, as processed during infection. Unfortunately, we could not confirm the biological relevance of protein targets for viral infections detected by MS. Thus, although mass spectrometry is highly sensitive and useful in many instances, also being able to show directions where cell/virus interaction occurs, we believe that deep recognition of their biological role is essential to receive complete insight into the investigated process.
质谱(MS)在蛋白质组学方法中能够在单次测定中检测数百种蛋白质。尽管 MS 的分析能力无可否认,但有时获取的数据会导致令人困惑的结果,特别是在复杂生物基质中搜索非常选择性、独特的相互作用时。在这里,我们将展示一个这样令人困惑的数据的例子,并对观察到的现象进行广泛的讨论。我们的研究集中在寨卡病毒 NS3 蛋白酶之间的相互作用上,这种蛋白酶对于病毒复制是必不可少的。这种酶以帮助重塑受感染细胞的微环境而闻名。有几项报告表明,这种蛋白酶可以处理细胞底物,从而修饰对病毒很重要的细胞途径。在这里,我们通过蛋白质组学技术探索了 NS3 的一些靶标,这些靶标在感染过程中被明显地处理。不幸的是,我们无法证实 MS 检测到的与病毒感染有关的蛋白质靶标具有生物学相关性。因此,尽管质谱在许多情况下高度敏感且有用,并且能够显示细胞/病毒相互作用发生的方向,但我们认为,深入认识其生物学作用对于全面了解所研究的过程是至关重要的。