HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production

El-Amine, R.; Germini, D.; Zakharova, V.V.; Tsfasman, T.; Sheval, E.V.; Louzada, R.A.; Dupuy, C.; Bilhou-Nabera, C.; Hamade, A.; Najjar, F.; Oksenhendler, E.; Lipinski, M.; Chernyak, B.V.; Vassetzky, Y.S.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 2 мая 2018 г.

Авторы: El-Amine R., Germini D., Zakharova V.V., Tsfasman T., Sheval E.V., Louzada R.A.N, Dupuy C., Bilhou-Nabera C., Hamade A., Najjar F., Oksenhendler E., Lipinski M., Chernyak B.V., Vassetzky Y.S.
Журнал: Redox Biology
Том: 15
Год издания: 2018
Первая страница: 97
Последняя страница: 108
DOI: 10.1016/j.redox.2017.11.024
Аннотация: Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals.
Добавил в систему: Шеваль Евгений Валерьевич

	ИСТИНА	Войти в систему Регистрация
	ИСТИНА ЦЭМИ РАН
	Главная Поиск Статистика О проекте Помощь

ИСТИНА

ИСТИНА ЦЭМИ РАН

HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS productionстатья

Прикрепленные файлы