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Biomedicines, volume 10, issue 7, pages 1697

In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells

Naumenko Victor A 1
Vishnevskiy Daniil A 1
Sosnovtseva Anastasiia O. 1
Chernysheva Anastasiia A 1
Valikhov Marat P. 1
Lipatova Anastasiia V 4
Chekhonin Vladimir P 1, 2
Publication typeJournal Article
Publication date2022-07-13
Journal: Biomedicines
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor4.7
ISSN22279059
General Biochemistry, Genetics and Molecular Biology
Medicine (miscellaneous)
Abstract

Hepatotoxicity remains an as yet unsolved problem for adenovirus (Ad) cancer therapy. The toxic effects originate both from rapid Kupffer cell (KCs) death (early phase) and hepatocyte transduction (late phase). Several host factors and capsid components are known to contribute to hepatotoxicity, however, the complex interplay between Ad and liver cells is not fully understood. Here, by using intravital microscopy, we aimed to follow the infection and immune response in mouse liver from the first minutes up to 72 h post intravenous injection of three Ads carrying delta-24 modification (Ad5-RGD, Ad5/3, and Ad5/35). At 15–30 min following the infusion of Ad5-RGD and Ad5/3 (but not Ad5/35), the virus-bound macrophages demonstrated signs of zeiosis: the formation of long-extended protrusions and dynamic membrane blebbing with the virus release into the blood in the membrane-associated vesicles. Although real-time imaging revealed interactions between the neutrophils and virus-bound KCs within minutes after treatment, and long-term contacts of CD8+ T cells with transduced hepatocytes at 24–72 h, depletion of neutrophils and CD8+ T cells affected neither rate nor dynamics of liver infection. Ad5-RGD failed to complete replicative cycle in hepatocytes, and transduced cells remained impermeable for propidium iodide, with a small fraction undergoing spontaneous apoptosis. In Ad5-RGD-immune mice, the virus neither killed KCs nor transduced hepatocytes, while in the setting of hepatic regeneration, Ad5-RGD enhanced liver transduction. The clinical and biochemical signs of hepatotoxicity correlated well with KC death, but not hepatocyte transduction. Real-time in vivo tracking for dynamic interactions between virus and host cells provides a better understanding of mechanisms underlying Ad-related hepatotoxicity.

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Naumenko V. A. et al. In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells // Biomedicines. 2022. Vol. 10. No. 7. p. 1697.
GOST all authors (up to 50) Copy
Naumenko V. A., Vishnevskiy D. A., Stepanenko A. A., Sosnovtseva A. O., Chernysheva A. A., Abakumova T. O., Valikhov M. P., Lipatova A. V., Abakumov M. A., Chekhonin V. P. In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells // Biomedicines. 2022. Vol. 10. No. 7. p. 1697.
RIS |
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RIS Copy
TY - JOUR
DO - 10.3390/biomedicines10071697
UR - https://doi.org/10.3390%2Fbiomedicines10071697
TI - In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells
T2 - Biomedicines
AU - Naumenko, Victor A
AU - Vishnevskiy, Daniil A
AU - Sosnovtseva, Anastasiia O.
AU - Chernysheva, Anastasiia A
AU - Valikhov, Marat P.
AU - Lipatova, Anastasiia V
AU - Chekhonin, Vladimir P
AU - Stepanenko, Aleksei A.
AU - Abakumova, Tatiana O
AU - Abakumov, Maxim A.
PY - 2022
DA - 2022/07/13 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 1697
IS - 7
VL - 10
PMID - 35885002
SN - 2227-9059
ER -
BibTex |
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BibTex Copy
@article{2022_Naumenko
author = {Victor A Naumenko and Daniil A Vishnevskiy and Anastasiia O. Sosnovtseva and Anastasiia A Chernysheva and Marat P. Valikhov and Anastasiia V Lipatova and Vladimir P Chekhonin and Aleksei A. Stepanenko and Tatiana O Abakumova and Maxim A. Abakumov},
title = {In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells},
journal = {Biomedicines},
year = {2022},
volume = {10},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {jul},
url = {https://doi.org/10.3390%2Fbiomedicines10071697},
number = {7},
pages = {1697},
doi = {10.3390/biomedicines10071697}
}
MLA
Cite this
MLA Copy
Naumenko, Victor A., et al. “In Vivo Tracking for Oncolytic Adenovirus Interactions with Liver Cells.” Biomedicines, vol. 10, no. 7, Jul. 2022, p. 1697. https://doi.org/10.3390%2Fbiomedicines10071697.
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