title: Entrance of the Tat protein of HIV-1 into human uterine cervical carcinoma cells causes upregulation of HPV-E6 expression and a decrease in p53 protein levels.
abstract: The infection of uterine cervical epithelial cells by oncogenic, high-risk human papilloma viruses (HR-HPVs) may lead to the development of cervical carcinoma. Of note, the incidence of this tumor is significantly increased in women infected by both HR-HPV and human immunodeficiency virus (HIV)-1. In this regard, previous studies have linked the HIV-1 Tat protein, a trans-activator of viral gene expression, to the pathogenesis of HIV-associated malignancies. In particular, it has been shown that upon its release by acutely infected cells, Tat protein can enter human cells, thus modifying their phenotype. Based on these findings, the present study evaluated whether extracellular Tat protein could be taken up by human uterine cervical carcinoma cells, and whether this could affect the expression of HPV (E6 or E7) or cellular (p16 or p53) molecules, which are key to cervical carcinoma development or progression. The results indicated that extracellular, biologically active HIV-1 Tat protein is taken up by human uterine cervical carcinoma cells, and that this is followed by an increase in the expression of the E6 protein of HPV, and by a reduction in the protein levels of the cellular oncosuppressor p53. Since p53 loss is associated with cell dedifferentiation and immortalization, these findings suggest a possible link between extracellular Tat protein and the high incidence and clinical aggressiveness of uterine cervical carcinoma observed in HIV/HPV doubly infected women.
authors.affiliation: Department of Clinical Sciences and Translational Medicine, University 'Tor Vergata', I-00133 Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barillari
authors.affiliation: National AIDS Center, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Palladino
authors.affiliation: National AIDS Center, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bacigalupo
authors.affiliation: National AIDS Center, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Leone
authors.affiliation: National AIDS Center, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.affiliation: National AIDS Center, National Institute of Health, I-00161 Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Ensoli
keywords: E6; HIV-1 Tat protein; human papilloma virus; p16; p53; uterine cervical carcinoma