Open Access

Oxidative Medicine and Cellular Longevity, volume 2019, pages 1-28

HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist

Bayurova Ekaterina ^{1, 2}

Jansons Juris ^{3, 4}

Skrastina Dace ^{3, 4}

Smirnova Olga ⁵

Mezale Dzeina ³

Kostyusheva Anastasia ⁶

Kostyushev Dmitry ⁶

Petkov Stefan ⁷

Podschwadt Philip ⁷

Valuev Elliston Vladimir ⁵

Sasinovich Sviataslau ⁷

Korolev Sergey P. ⁸

Warholm Per ⁹

Латанова А. А. ^{2, 5}

Starodubova Elizaveta S. ^{2, 5}

Tukhvatulin Amir I. ²

Latyshev Oleg ²

Selimov Renat ¹⁰

Metalnikov Pavel ¹⁰

Komarov Alexander ¹⁰

Ivanova Olga ⁵

Gorodnicheva Tatiana ¹¹

Кочетков С. Н. ⁵

Gottikh Marina ⁸

Strumfa Ilze ³

Ivanov Alexander ⁵

Gordeychuk Ilya ^{1, 2, 12}

Isaguliants Maria G. ^{1, 2, 3, 7}

Hide authors affiliations Show authors affiliations: 12 affiliations

Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, Moscow, Russia |

NF Gamaleya Research Center of Epidemiology and Microbiology, Moscow, Russia |

Department of Pathology, Riga Stradins University, Riga, Latvia |

⁴

Latvian Biomedical Research and Study centre, Riga, Latvia |

⁵

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia |

⁶

National Medical Research Center for Tuberculosis and Infectious Diseases, Moscow, Russia |

⁷

Department of Microbiology, Tumor and Cell biology, Karolinska Institutet, Stockholm, Sweden |

⁸

Chemistry Department and Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia |

⁹

Science for Life Laboratory, Stockholm University, Stockholm, Sweden |

¹⁰

Russian State Center for Quality and Standardization of Veterinary Drugs and Feed (VGNKI), Moscow, Russia |

¹¹

Evrogen, Moscow, Russia |

¹²

Sechenov first moscow state medical university, Moscow, Russia |

Publication type: Journal Article

Publication date: 2019-12-02

Hindawi Limited

Journal: Oxidative Medicine and Cellular Longevity

Quartile SCImago

Quartile WOS

—

Impact factor: —

ISSN: 19420900, 19420994

DOI: 10.1155/2019/6016278

Copy DOI

PubMed ID: 31885806

Biochemistry

General Medicine

Cell Biology

Ageing

Abstract

HIV-induced immune suppression results in the high prevalence of HIV/AIDS-associated malignancies including Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer. HIV-infected people are also at an increased risk of “non-AIDS-defining” malignancies not directly linked to immune suppression but associated with viral infections. Their incidence is increasing despite successful antiretroviral therapy. The mechanism behind this phenomenon remains unclear. Here, we obtained daughter clones of murine mammary gland adenocarcinoma 4T1luc2 cells expressing consensus reverse transcriptase of HIV-1 subtype A FSU_A strain (RT_A) with and without primary mutations of drug resistance. Inin vitrotests, mutations of resistance to nucleoside inhibitors K65R/M184V reduced the polymerase, and to nonnucleoside inhibitors K103N/G190S, the RNase H activities of RT_A. Expression of these RT_A variants in 4T1luc2 cells led to increased production of the reactive oxygen species (ROS), lipid peroxidation, enhanced cell motility in the wound healing assay, and upregulation of expression ofVimentinandTwist. These properties, particularly, the expression ofTwist, correlated with the levels of expression RT_A and/or the production of ROS. When implanted into syngeneic BALB/C mice, 4T1luc2 cells expressing nonmutated RT_A demonstrated enhanced rate of tumor growth and increased metastatic activity, dependent on the level of expression of RT_A andTwist. No enhancement was observed for the clones expressing mutated RT_A variants. Plausible mechanisms are discussed involving differential interactions of mutated and nonmutated RTs with its cellular partners involved in the regulation of ROS. This study establishes links between the expression of HIV-1 RT, production of ROS, induction of EMT, and enhanced propagation of RT-expressing tumor cells. Such scenario can be proposed as one of the mechanisms of HIV-induced/enhanced carcinogenesis not associated with immune suppression.

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Bayurova E. et al. HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist // Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019. pp. 1-28.

GOST all authors (up to 50) Copy

Bayurova E., Jansons J., Skrastina D., Smirnova O., Mezale D., Kostyusheva A., Kostyushev D., Petkov S., Podschwadt P., Valuev Elliston V., Sasinovich S., Korolev S. P., Warholm P., Латанова А. А., Starodubova E. S., Tukhvatulin A. I., Latyshev O., Selimov R., Metalnikov P., Komarov A., Ivanova O., Gorodnicheva T., Кочетков С. Н., Gottikh M., Strumfa I., Ivanov A., Gordeychuk I., Isaguliants M. G. HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist // Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019. pp. 1-28.

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RIS Copy

TY - JOUR

DO - 10.1155/2019/6016278

UR - https://doi.org/10.1155%2F2019%2F6016278

TI - HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist

T2 - Oxidative Medicine and Cellular Longevity

AU - Bayurova, Ekaterina

AU - Jansons, Juris

AU - Skrastina, Dace

AU - Mezale, Dzeina

AU - Kostyusheva, Anastasia

AU - Kostyushev, Dmitry

AU - Petkov, Stefan

AU - Podschwadt, Philip

AU - Valuev Elliston, Vladimir

AU - Sasinovich, Sviataslau

AU - Korolev, Sergey P.

AU - Warholm, Per

AU - Латанова, А. А.

AU - Starodubova, Elizaveta S.

AU - Tukhvatulin, Amir I.

AU - Latyshev, Oleg

AU - Metalnikov, Pavel

AU - Komarov, Alexander

AU - Ivanova, Olga

AU - Gorodnicheva, Tatiana

AU - Кочетков, С. Н.

AU - Strumfa, Ilze

AU - Ivanov, Alexander

AU - Gordeychuk, Ilya

AU - Isaguliants, Maria G.

AU - Selimov, Renat

AU - Gottikh, Marina

AU - Smirnova, Olga

PY - 2019

DA - 2019/12/02 00:00:00

PB - Hindawi Limited

SP - 1-28

VL - 2019

PMID - 31885806

SN - 1942-0900

SN - 1942-0994

ER -

BibTex

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BibTex Copy

@article{2019_Bayurova,

author = {Ekaterina Bayurova and Juris Jansons and Dace Skrastina and Dzeina Mezale and Anastasia Kostyusheva and Dmitry Kostyushev and Stefan Petkov and Philip Podschwadt and Vladimir Valuev Elliston and Sviataslau Sasinovich and Sergey P. Korolev and Per Warholm and А. А. Латанова and Elizaveta S. Starodubova and Amir I. Tukhvatulin and Oleg Latyshev and Pavel Metalnikov and Alexander Komarov and Olga Ivanova and Tatiana Gorodnicheva and С. Н. Кочетков and Ilze Strumfa and Alexander Ivanov and Ilya Gordeychuk and Maria G. Isaguliants and Renat Selimov and Marina Gottikh and Olga Smirnova},

title = {HIV-1 Reverse Transcriptase Promotes Tumor Growth and Metastasis Formation via ROS-Dependent Upregulation of Twist},

journal = {Oxidative Medicine and Cellular Longevity},

year = {2019},

volume = {2019},

publisher = {Hindawi Limited},

month = {dec},

url = {https://doi.org/10.1155%2F2019%2F6016278},

pages = {1--28},

doi = {10.1155/2019/6016278}

}

Found error?

Publisher

Hindawi Limited

Journal

Oxidative Medicine and Cellular Longevity

Quartile SCImago

Quartile WOS

—

Impact factor

—

ISSN

19420900 (Print)
19420994 (Electronic)

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