Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind
No Thumbnail Available
Date
2021-01-02
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
People living with human immunodeficiency virus (HIV-1) are at increased risk of developing cancer, such as Kaposi sarcoma (KS), non-Hodgkin lymphoma (NHL), cervical cancer, and other cancers associated with chronic viral infections. Traditionally, this is linked to HIV-1-induced immune suppression with depletion of CD4+ T-helper cells, exhaustion of lymphopoiesis and lymphocyte dysfunction. However, the long-term successful implementation of antiretroviral therapy (ART) with an early start did not preclude the oncological complications, implying that HIV-1 and its antigens are directly involved in carcinogenesis and may exert their effects on the background of restored immune system even when present at extremely low levels. Experimental data indicate that HIV-1 virions and single viral antigens can enter a wide variety of cells, including epithelial. This review is focused on the effects of five viral proteins: envelope protein gp120, accessory protein negative factor Nef, matrix protein p17, transactivator of transcription Tat and reverse transcriptase RT. Gp120, Nef, p17, Tat, and RT cause oxidative stress, can be released from HIV-1-infected cells and are oncogenic. All five are in a position to affect “innocent” bystander cells, specifically, to cause the propagation of (pre)existing malignant and malignant transformation of normal epithelial cells, giving grounds to the direct carcinogenic effects of HIV-1.
Description
Funding Information: Funding: This study was supported the Russian Fund for Basic Research grants 17_54_30002 and 20‐04‐01034 to M.I., Latvian Science Council grants LZP‐2018/2‐0308 and LZP‐2020/2‐0376 to M.I., Funding Information: and NCI R01CA 217715 to J.P.The work of Francesca Chiodi is supported by a grant from the Swe‐ dish Medical Research Council (Francesca Chiodi; Vetenskapsrådet 2019‐01169). Publisher Copyright: © 2021 by the authors.
Keywords
human immunodeficiency virus type 1, epithelial cells, carcinogenicity, oxidative stress, reactive oxygen species, gp120, Tat, Nef, matrix protein p17, reverse transcriptase, 3.2 Clinical medicine, 1.1. Scientific article indexed in Web of Science and/or Scopus database, SDG 3 - Good Health and Well-being
Citation
Isaguliants, M, Bayurova, E, Avdoshina, D, Kondrashova, A, Chiodi, F & Palefsky, J M 2021, 'Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind', Cancers, vol. 13, no. 2, 305, pp. 1-24. https://doi.org/10.3390/cancers13020305