In vivo cell tracking with viral vector mediated genetic labeling

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Highlights

  • Genetical labeling of the target cells is a key approach for in vivo cell tracking.

  • Viruses are natural vehicles to deliver and express exogenous genes in host cells.

  • Viral vectors facilitate cell labeling by expressing reporter protein.

  • Many viruses can be genetically modified into reporter protein-expressing vectors.

  • Cells labeled via viral vectors can be tracked in vivo to achieve multiple purposes.

Abstract

Cell tracking is a useful technique to monitor specific cell populations for their morphology, development, proliferation, migration, interaction, function, and other properties, both in vitro and in vivo. Using different materials and methodologies to label the target cells directly or indirectly, the dynamic biological processes in living organisms can be visualized with appropriate detection techniques. Viruses, with the unique ability to deliver exogenous genes into host cells, have been used as vectors to mediate gene transfer. Genetic labeling of target cells by viral vectors endows the cells to express reporter genes with high efficiency and specificity. In conjunction with corresponding imaging techniques, cells labeled with different genetic reporters mediated by different viral vectors can be monitored across spatial and temporal scales to fulfill various purposes and address different questions. In the present review, we introduce the basic principle of viral vectors in cell tracking and highlight the examples of cell tracking in various research areas.

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).

References (87)

  • S.J. Russell et al.

    Remission of disseminated cancer after systemic oncolytic virotherapy

    Mayo Clin. Proc.

    (2014)
  • N. Suff et al.

    The power of bioluminescence imaging in understanding host-pathogen interactions

    Methods

    (2017)
  • J.E. Sulston et al.

    The embryonic cell lineage of the nematode Caenorhabditis elegans

    Dev. Biol. (Basel)

    (1983)
  • S. Sun et al.

    Engineered viral vectors for functional interrogation, deconvolution, and manipulation of neural circuits

    Curr. Opin. Neurobiol.

    (2018)
  • T. VandenDriessche et al.

    Lentiviral vectors containing the human immunodeficiency virus type-1 central polypurine tract can efficiently transduce nondividing hepatocytes and antigen-presenting cells in vivo

    Blood

    (2002)
  • H. Wang et al.

    Lighting up the brain: genetically encoded fluorescent sensors for imaging neurotransmitters and neuromodulators

    Curr. Opin. Neurobiol.

    (2018)
  • X. Xu et al.

    Viral vectors for neural circuit mapping and recent advances in trans-synaptic anterograde tracers

    Neuron

    (2020)
  • L.J. Zhang et al.

    Lipid-specific labeling of enveloped viruses with quantum dots for single-virus tracking

    mBio

    (2020)
  • D.R. Beckford Vera et al.

    Immuno-PET imaging of tumor-infiltrating lymphocytes using zirconium-89 radiolabeled anti-CD3 antibody in immune-competent mice bearing syngeneic tumors

    PLoS One

    (2018)
  • M. Bouvet et al.

    In vivo color-coded imaging of the interaction of colon cancer cells and splenocytes in the formation of liver metastases

    Cancer Res.

    (2006)
  • E.A. Caine et al.

    In vivo imaging with bioluminescent enterovirus 71 allows for real-time visualization of tissue tropism and viral spread

    J. Virol.

    (2017)
  • J.P. Card et al.

    A dual infection pseudorabies virus conditional reporter approach to identify projections to collateralized neurons in complex neural circuits

    PLoS One

    (2011)
  • J.P. Card et al.

    Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus

    Proc. Natl. Acad. Sci. U. S. A.

    (2011)
  • J.D. Clarke et al.

    Fate maps old and new

    Nat. Cell Biol.

    (1999)
  • D.K. Cureton et al.

    Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures

    J. Virol.

    (2012)
  • K. Dobrenkov et al.

    Monitoring the efficacy of adoptively transferred prostate cancer-targeted human T lymphocytes with PET and bioluminescence imaging

    J. Nucl. Med.

    (2008)
  • K.L. Farina et al.

    Cell motility of tumor cells visualized in living intact primary tumors using green fluorescent protein

    Cancer Res.

    (1998)
  • G.S. Filonov et al.

    Bright and stable near-infrared fluorescent protein for in vivo imaging

    Nat. Biotechnol.

    (2011)
  • G.O. Fruhwirth et al.

    A whole-body dual-modality radionuclide optical strategy for preclinical imaging of metastasis and heterogeneous treatment response in different microenvironments

    J. Nucl. Med.

    (2014)
  • M.J. Gething et al.

    Cell-surface expression of influenza haemagglutinin from a cloned DNA copy of the RNA gene

    Nature

    (1981)
  • D.A. Gibson et al.

    Mosaic analysis of gene function in postnatal mouse brain development by using virus-based Cre recombination

    J. Vis. Exp.

    (2011)
  • M.G. Haberl et al.

    An anterograde rabies virus vector for high-resolution large-scale reconstruction of 3D neuron morphology

    Brain Struct. Funct.

    (2015)
  • D. Haddad et al.

    Molecular imaging of oncolytic viral therapy

    Mol. Ther. Oncolytics

    (2015)
  • M.P. Hall et al.

    Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate

    ACS Chem. Biol.

    (2012)
  • L. Hu et al.

    The major hurdle for effective baculovirus transduction into mammalian cells is passing early endosomes

    J. Virol.

    (2019)
  • A.H. Jacobs et al.

    Improved herpes simplex virus type 1 amplicon vectors for proportional coexpression of positron emission tomography marker and therapeutic genes

    Hum. Gene Ther.

    (2003)
  • F. Jia et al.

    Rapid and sparse labeling of neurons based on the mutant virus-like particle of semliki forest virus

    Neurosci. Bull.

    (2019)
  • M. Jing et al.

    A genetically encoded fluorescent acetylcholine indicator for in vitro and in vivo studies

    Nat. Biotechnol.

    (2018)
  • H.S. Kim et al.

    In vivo tracking of dendritic cell using MRI reporter gene

    Ferritin. PLoS One

    (2015)
  • J. Kirui et al.

    Generation and validation of a highly sensitive bioluminescent HIV-1 reporter vector that simplifies measurement of virus release

    Retrovirology

    (2020)
  • G. Koehne et al.

    Serial in vivo imaging of the targeted migration of human HSV-TK-transduced antigen-specific lymphocytes

    Nat. Biotechnol.

    (2003)
  • H.W. Lee et al.

    Tracking of dendritic cell migration into lymph nodes using molecular imaging with sodium iodide symporter and enhanced firefly luciferase genes

    Sci. Rep.

    (2015)
  • J. Li et al.

    Trans-synaptic neural circuit-tracing with neurotropic viruses

    Neurosci. Bull.

    (2019)
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