HIV-1 Tat and AIDS-associated cancer: targeting the cellular anti-cancer barrier?

Abstract

The acquired immunodeficiency syndrome (AIDS) is accompanied by a significant increase in the incidence of neoplasms. Several causative agents have been proposed for this phenomenon. These include immunodeficiency and oncogenic DNA viruses and the HIV-1 protein Tat. Cancer in general is closely linked to genomic instability and DNA repair mechanisms. The latter maintains genomic stability and serves as a cellular anti-cancer barrier. Defects in DNA repair pathway are associated with carcinogenesis.This review focuses on newly discovered connections of the HIV-1 protein Tat, as well as cellular co-factors of Tat, to double-strand break DNA repair. We propose that the Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

“…Evidence also indicates that Tat can activate the expression of a number of heterologous viral promoters, such as herpes viruses, HTLV-1 and -2, JC, and others, implying that Tat may be also involved in the development of AIDS-associated opportunistic infections. Finally, the Tat protein, both intracellular and extracellular, exerts key roles in the pathogenesis of AIDS-associated tumors [100,102] and AIDS-associated neuropathogenesis [103]. The first exon of Tat encodes aminoacids 1-72, which include the N-terminal prolinerich (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], the cysteine-rich (aa 21-37 containing 7 cysteines) and the core (aa 38-48) regions, representing Tat activation domain, and the basic region (aa 49-58) for nuclear localization and binding to the HIV LTR TAR RNAs.…”

Giant cell carcinoma causing rapidly progressive respiratory failure as the presenting feature of AIDS

“…Recently, the HIV-1 protein Tat, as well as cellular co-factors of Tat, has been reported to be associated with impairment of double-strand break DNA repair. 13,14 Defects in the DNA repair pathway are associated with carcinogenesis. Thus, Tat-induced DNA repair deficiencies may play a significant role in the development of AIDS-associated cancer.…”

Targeting HIV Transcription: The Quest for a Functional Cure

“…Tat’s basic domain and cysteine-rich region could play an important role in these neurotoxic effects (Li et al 2009), and patients infected with HIV-1 subtype C, containing a mutation in Tat’s cysteine region, tend to have less prevalence of HAND (Li et al 2009). Extracellular Tat has also been associated with acquired immune deficiency syndrome (AIDS)-associated cancers such as Kaposi’s sarcoma, often developing more aggressively in HIV-infected patients (Johri et al 2011; Nunnari et al 2008; Romani et al 2010). Tat’s basic domain, by competing with basic fibroblast growth factor for heparin sulfate proteoglycan, may induce spindle cell growth in Kaposi’s sarcoma (Campbell and Loret 2009).…”