View and review on viral oncology research

To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/). According to the World Health Organization (WHO), roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens

Studio dei meccanismi molecolari alla base del coinvolgimento della proteina NEF di HIV-1 nella demenza associata ad HIV-1 (HAD)

During HIV-1 associated dementia (HAD), a variety of HIV-1-induced lesions of the central nervous system (CNS) has been described, including neuronal loss, but very little is known about the mechanisms that lead to this process. Among HIV-1 proteins, we analysed the role of Nef since it could alter some signal transduction pathways related to cellular proteins involved in neuronal differentiation, such as ALK (Anaplastic Lymphoma Kinase), thus contributing to explain some of the HAD features. Our data show that Nef alters ALK expression and interferes with the ALK signal transduction pathway, in particular by modifying the MMP-9 (Matrix MetalloProteinase-9) and MMP-2 (Matrix MetalloProteinase-2) pathways. Furthermore, Nef and ALK show a cumulative effect in the modulation of cytochines/chemokines and of proteins involved in their common transduction pathways, such as MAP-K

Nef and cell signaling transduction: a possible involvement in the pathogenesis of human immunodeficiency virus-associated dementia

Although the introduction of highly active antiretroviral therapy (HAART) has resulted in a significant decrease of acquired immunodeficiency syndrome (AIDS) morbidity and mortality, the prevalence of human immunodeficiency virus (HIV)-associated dementia (HAD) has actually risen, due to the increasing life expectancy of the infected subjects. To date, several aspects of the HAD pathogenesis remain to be dissected. In particular, the viral-cellular protein interplay is still under investigation. Given their specific features, two viral proteins, Tat and Nef, have been mainly hypothesized to play a role in HIV neuropathology. Here we show that HIV-1 Nef has an effect on the transcriptional levels of a cellular protein, anaplastic lymphoma kinase (ALK), that is preferentially expressed in the central and peripheral nervous system at late embryonic stages. By its overexpression along with Nef, the authors demonstrate ALK ability to influence, at least in the U87MG astrocytic glioma cells, the mytogen-activated protein kinase (MAP-K)-dependent pathway. Moreover, although in the absence of a physical direct interaction, Nef and ALK activate matrix metalloproteinases (MMPs), which are likely to contribute to blood-brain barrier (BBB) damage in HAD. Finally, in the in vitro model of glioblastoma cells adopted, Nef and ALK show similar effects by increasing different cytochines/chemokines that may be relevant for HAD pathogenesis. If confirmed in vivo, these data may indicate that, thanks to its ability to interfere with specific cellular pathways involved in BBB damage and in central nervous system (CNS) integrity, Nef, along with specific cellular counterparts, could be one of the viral players implicated in HAD development