Spatiotemporal Quantification of Endosomal Acidification on the Viral Journey
Zhi-Gang Wang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLiang Zhao
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLu-Lu Chen
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorHao-Yang Liu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLei Wang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorYusi Hu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorXue-Hui Shi
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorDongbing Zhao
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorCorresponding Author
Shu-Lin Liu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074 P. R. China
E-mail: [email protected]
Search for more papers by this authorDai-Wen Pang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorZhi-Gang Wang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLiang Zhao
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLu-Lu Chen
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorHao-Yang Liu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorLei Wang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorYusi Hu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorXue-Hui Shi
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorDongbing Zhao
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorCorresponding Author
Shu-Lin Liu
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences, Wuhan, 430074 P. R. China
E-mail: [email protected]
Search for more papers by this authorDai-Wen Pang
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Research Center for Analytical Sciences, College of Chemistry, and School of Medicine, Nankai University, Tianjin, 300071 P. R. China
Search for more papers by this authorAbstract
Many enveloped viruses utilize endocytic pathways and vesicle trafficking to infect host cells, where the acidification of virus-containing endosomes triggers the virus-endosome fusion events. Therefore, simultaneous correlation of intracellular location, local pH, and individual virus dynamics is important for gaining insight into viral infection mechanisms. Here, an imaging approach is developed for spatiotemporal quantification of endosomal acidification on the viral journey in host cells using a fluorescence resonance energy transfer based ratiometric pH sensor consisting of a photostable and high-brightness QD, pH-sensitive fluorescent dyes, and virus-binding proteins. Ratiometric analysis of sensor-based single-virus tracking data enables to dissect a two-step endosomal acidification process during the infection of influenza viruses and elucidates the occurrence of the fission and sorting of virus-containing endosomes to recycling endosomes after initial acidification. This technique should serve as a robust approach for in situ quantification of endosomal acidification on the viral journey.
Conflict of Interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
Research data are not shared.
Supporting Information
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smll202104200-sup-0001-SuppMat.pdf999.9 KB | Supporting Information |
smll202104200-sup-0002-MovieS1.mp4349.9 KB | Supplemental Movie 1 |
smll202104200-sup-0003-MovieS2.mp4319.2 KB | Supplemental Movie 2 |
smll202104200-sup-0004-MovieS3.mp43 MB | Supplemental Movie 3 |
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References
- 1U. F. Greber, M. Way, Cell 2006, 124, 741.
- 2S. B. Sieczkarski, G. R. Whittaker, J. Gen. Virol. 2002, 83, 1535.
- 3W. Mothes, A. L. Boerger, S. Narayan, J. M. Cunningham, J. A. Young, Cell 2000, 103, 679.
- 4M. Lakadamyali, M. J. Rust, H. P. Babcock, X. Zhuang, Proc. Natl. Acad. Sci. USA 2003, 100, 9280.
- 5M. Lakadamyali, M. J. Rust, X. Zhuang, Microbes Infect. 2004, 6, 929.
- 6M. Kielian, F. A. Rey, Nat. Rev. Microbiol. 2006, 4, 67.
- 7G. B. Melikyan, R. J. Barnard, R. M. Markosyan, J. A. Young, F. S. Cohen, J. Virol. 2004, 78, 3753.
- 8S. Padilla-Parra, M. Marin, N. Kondo, G. B. Melikyan, Retrovirology 2014, 11, 47.
- 9S. Padilla-Parra, P. M. Matos, N. Kondo, M. Marin, N. C. Santos, G. B. Melikyan, Proc. Natl. Acad. Sci. USA 2012, 109, 17627.
- 10K. Miyauchi, Y. Kim, O. Latinovic, V. Morozov, G. B. Melikyan, Cell 2009, 137, 433.
- 11S. L. Liu, Z. G. Wang, H. Y. Xie, A. A. Liu, D. C. Lamb, D. W. Pang, Chem. Rev. 2020, 120, 1936.
- 12S. L. Liu, Z. G. Wang, Z. L. Zhang, D. W. Pang, Chem. Soc. Rev. 2016, 45, 1211.
- 13L. J. Zhang, L. Xia, S. L. Liu, E. Z. Sun, Q. M. Wu, L. Wen, Z. L. Zhang, D. W. Pang, ACS Nano 2018, 12, 474.
- 14Q. M. Wu, S. L. Liu, G. Chen, W. Zhang, E. Z. Sun, G. F. Xiao, Z. L. Zhang, D. W. Pang, Small 2018, 14, 1702841.
- 15E. Z. Sun, A. A. Liu, Z. L. Zhang, S. L. Liu, Z. Q. Tian, D. W. Pang, ACS Nano 2017, 11, 4395.
- 16S. L. Liu, Z. L. Zhang, Z. Q. Tian, H. S. Zhao, H. Liu, E. Z. Sun, G. F. Xiao, W. Zhang, H. Z. Wang, D. W. Pang, ACS Nano 2012, 6, 141.
- 17H. Liu, Y. Liu, S. Liu, D. W. Pang, G. Xiao, J. Virol. 2011, 85, 6252.
- 18L. J. Zhang, L. Xia, H. Y. Xie, Z. L. Zhang, D. W. Pang, Anal. Chem. 2019, 91, 532.
- 19C. Qin, W. Li, Q. Li, W. Yin, X. Zhang, Z. Zhang, X. E. Zhang, Z. Cui, Proc. Natl. Acad. Sci. USA 2019, 116, 2577.
- 20R. Freeman, I. Willner, Chem. Soc. Rev. 2012, 41, 4067.
- 21C. Xia, W. Wang, L. Du, F. T. Rabouw, D. J. van den Heuvel, H. C. Gerritsen, H. Mattoussi, C. de Mello Donega, J. Phys. Chem. C 2019, 124, 1717.
- 22Y. J. Gong, X. B. Zhang, G. J. Mao, L. Su, H. M. Meng, W. Tan, S. Feng, G. Zhang, Chem. Sci. 2016, 7, 2275.
- 23Y. J. Gong, Z. Z. Kong, M.-L. Zhang, M. K. Lv, G. Zhang, Talanta 2019, 203, 1.
- 24M. Maekawa, Sensors 2017, 17, 504.
- 25M. Maekawa, Y. Yang, G. D. Fairn, Toxins 2016, 8, 67.
- 26S. L. Liu, R. Sheng, J. H. Jung, L. Wang, E. Stec, M. J. O'Connor, S. Song, R. K. Bikkavilli, R. A. Winn, D. Lee, K. Baek, K. Ueda, I. Levitan, K. P. Kim, W. Cho, Nat. Chem. Biol. 2017, 13, 268.
- 27S. L. Liu, Z. Q. Tian, Z. L. Zhang, Q. M. Wu, H. S. Zhao, B. Ren, D. W. Pang, Biomaterials 2012, 33, 7828.
- 28Q. Li, A. Lau, T. J. Morris, L. Guo, C. B. Fordyce, E. F. Stanley, J. Neurosci. 2004, 24, 4070.
- 29S. Vale-Costa, M. J. Amorim, Viruses 2016, 8, 64.
- 30S. L. Liu, Q. M. Wu, L. J. Zhang, Z. G. Wang, E. Z. Sun, Z. L. Zhang, D. W. Pang, Small 2014, 10, 4746.
- 31Z. G. Wang, S. L. Liu, Z. L. Zhang, Z. Q. Tian, H. W. Tang, D. W. Pang, Small 2014, 10, 2712.
- 32J. R. Casey, S. Grinstein, J. Orlowski, Nat. Rev. Mol. Cell Biol. 2010, 11, 50.
- 33S. Li, C. Sieben, K. Ludwig, C. T. Hofer, S. Chiantia, A. Herrmann, F. Eghiaian, I. A. Schaap, Biophys. J. 2014, 106, 1447.