In vivo cell tracking with viral vector mediated genetic labeling
Graphical abstract
Introduction
In vivo cell tracking is an important and powerful technique to identify the structure, localization, migration and/or other properties of specific cell populations in living organisms. This technique has been applied in various research areas and contributed to great achievements, such as in virology, immunology, developmental biology, stem cell research, cancer research, and neuroscience. Many novel strategies and methods keep being developed in this flourishing research field for in vivo cell tracking. In general, the main principle is to label the target cells, and then monitor the labeled cells using appropriate detection techniques to achieve the specific investigation purposes.
Section snippets
Cell labeling
The imaging techniques are essential for in vivo cell tracking. However, properly labeling the target cells represents another indispensable key step for monitoring the cells in real-time, with no less importance than imaging. Currently, there are two major strategies applied to label the target cells for in vivo tracking: direct labeling and indirect labeling.
Viral vectors
Viruses are intracellular obligate parasitic microorganisms that utilize host cellular machinery to produce progenies in living organisms. The natural feature of specifically targeting cells and expressing the foreign gene in host cells makes viruses great potential to be utilized as vectors for gene delivery. In 1981, Gething and Sambrook constructed a recombinant simian vacuolating virus 40 (SV40), and used it to express haemagglutinin glycoprotein of the influenza A virus (IAV) on the cell
Investigating virus-host interactions
Human beings have always suffered from various kinds of infectious diseases, mild, severe, or even life-threatening, most of which are caused by viruses. Especially in recent decades, the explosion of many emerging and re-emerging viruses have sounded the alarm, such as influenza virus, Ebola virus, Zika virus, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the on-going SARS-CoV-2, etc. It calls for efficient methods to
Tracking immune cells
In the cases of viral infection, antiviral immune responses play a key role in controlling infection progression and disease deterioration. In vivo cell tracking of the immune cells can document not only the movement of immune cells within specific tissues or whole bodies in real-time but also the interactions of immune cells with virus or virus-infected-cells. Many strategies have been developed to label immune cells, such as antibody labeling, fluorescent dyeing, FP expression (McCarthy et
Evaluating tumor progression
Long-term observation of tumor cells in vivo is indispensable for cancer diagnosis and treatment assessment. For this purpose, the tumor cells are to be labeled with strong and sustained imaging markers. Due to the fast proliferation of tumor cells, conventional labeling with organic dye will be diluted along with cell division. Viral vectors have been commonly used to label tumor cells, especially retrovirus and lentivirus which mediated the persistent expression of reporter genes. Since
Analyzing cell lineage
Fundamental development is an essential research area that explores how a sophisticated organism is developed from an embryo. Early scientists used light microscopes to map cell lineage of little transparent animals, such as Caenorhabditis elegans (Sulston et al., 1983). However, it is scarcely possible to map cell lineage of mammals (e.g. the mouse) only by light microscope. Dyes, such as lipophilic dyes DiI and DiA which label plasma membrane, were used to track cell lineage (Clarke and
Mapping neural circuits
Neuroscience is one of the most focused research areas. The differentiation and migration of neural progenitor cells can be tracked using a similar strategy of linear monitoring. For example, Xiong et al. labeled the neural stem cells using FPs via viral vectors, and monitored their differentiation, axonal innervation, and integration into the neural network after transplanting them into mouse brains (Xiong et al., 2020). Mapping the function-associated brain network represents another key work
Summary
Although tremendous developments in the fields of biology have been accomplished with the conventional viral vectors, they all have limitations. For example, the small transgene capacity of AAV, pro-inflammatory of adenovirus, and potential oncogenicity of retrovirus/lentivirus. It requires further exploitation of new viral vectors to genetic engineering. The fast-developing viral vectors like HSV-1 based amplicon, measles virus, vesicular stomatitis virus, and cytomegalovirus have exhibited
Author contributions
YL and LY prepared the reference library and drafted the manuscript. SZ and MHL offered important support in preparing the manuscript. WBZ and FZ edited and commented on the manuscript.
Declaration of Competing Interest
The authors declare no competing interests.
Acknowledgment
This work was supported by the grant from the National Natural Science Foundation of China (1871660).
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