Human polyomaviruses (HPyV), which are small DNA viruses classified into the polyomaviridae family, are widely distributed in human populations. Thirteen distinct HPyVs have been described to date. Some of these viruses have been found in human tumors, suggesting an etiological relationship with cancer. In particular, convincing evidence of an oncogenic role has emerged for a specific HPyV, the Merkel cell polyomavirus (MCPyV). This HPyV has been linked to rare skin cancer, Merkel cell carcinoma (MCC). This finding may be just the tip of the iceberg, as HPyV infections are ubiquitous in humans. Many authors have conjectured that additional associations between HPyV infections and neoplastic diseases will likely be discovered. In 2012, the International Agency for Research on Cancer (IARC) evaluated the carcinogenicity of the BK virus (BKPyV), reporting that BKPyV is “possibly carcinogenic to humans.” This review explores the BKPyV infection from a historical point of view, including biological aspects related to viral entry, tropism, epidemiology and mechanisms potentially involved in BKPyV-mediated human carcinogenesis. In order to clarify the role of this virus in human cancer, more epidemiological and basic research is strongly warranted.

A subset of oral carcinomas is etiologically related to high-risk human papillomavirus (HR-HPV) infection, with HPV16 being the most frequent HR-HPV type found in these carcinomas. The oncogenic role of HR-HPV is strongly dependent on the overexpression of E6 and E7 oncoproteins, which, in turn, induce p53 and pRb degradation, respectively. Additionally, it has been suggested that HR-HPV oncoproteins are involved in the regulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inducing cancer progression and metastasis. Previously, we reported that HPV16 E7 oncoprotein promotes Pirin upregulation resulting in increased epithelial–mesenchymal transition (EMT) and cell migration, with Pirin being an oxidative stress sensor and activator of NF-κB. In this study, we demonstrate the mechanism by which HPV16 E7-mediated Pirin overexpression occurs by promoting EGFR/PI3K/AKT1/NRF2 signaling, thus causing PIR/NF-κB activation in oral tumor cells. Our results demonstrate a new mechanism by which E7 contributes to oral cancer progression, proposing PIR as a potential new therapeutic target.

Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein–protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.