Oncogenic Effects of HIV-1 Proteins, Mechanisms Behind.

Abstract

Simple SummaryPeople living with human immunodeficiency virus type 1 (HIV-1) (PLWH) are at increased risk of developing cancer despite successful antiretroviral therapy (ART). Here, authors suggest novel mechanism behind this phenomenon. HIV proteins, namely envelope protein gp120, accessory protein negative factor Nef, matrix protein p17, transactivator of transcription Tat and reverse transcriptase RT, are known to be oncogenic per se, to induce oxidative stress and to be released from the infected or expressing cells. These properties are proposed to underlie their capacity to affect bystander epithelial cells causing their malignant transformation, and to enhance tumorigenic potential of already transformed/cancer cells. HIV proteins can act alone or in collaboration with other known oncoproteins, specifically originating from the oncogenic human viruses such as human hepatitis B and C viruses, and human papilloma viruses of high carcinogenic risk, which cause the bulk of malignancies in people living with HIV-1 on ART. 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.