Lentiviral Vectors as Tools for the Study and Treatment of Glioblastoma

Glioblastoma (GBM) has the worst prognosis among brain tumors, hence basic biology, preclinical, and clinical studies are necessary to design effective strategies to defeat this disease. Gene transfer vectors derived from the most-studied lentivirus-the Human Immunodeficiency Virus type 1-have wide application in dissecting GBM specific features to identify potential therapeutic targets. Last-generation lentiviruses (LV), highly improved in safety profile and gene transfer capacity, are also largely employed as delivery systems of therapeutic molecules to be employed in gene therapy (GT) approaches. LV were initially used in GT protocols aimed at the expression of suicide factors to induce GBM cell death. Subsequently, LV were adopted to either express small noncoding RNAs to affect different aspects of GBM biology or to overcome the resistance to both chemo- and radiotherapy that easily develop in this tumor after initial therapy. Newer frontiers include adoption of LV for engineering T cells to express chimeric antigen receptors recognizing specific GBM antigens, or for transducing specific cell types that, due to their biological properties, can function as carriers of therapeutic molecules to the cancer mass. Finally, LV allow the setting up of improved animal models crucial for the validation of GBM specific therapies

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

How to break free: HIV-1 escapes from innovative therapeutic approaches

With nearly 38 million of people worldwide living with HIV-1 and no definitive cure available after almost 40 years of research, AIDS is still a major global public health issue. Modern antiretroviral therapies can achieve viral replication suppression to undetectable levels, thus allowing an almost normal life to HIV-1–infected individuals. However, the virus cannot be fully eradicated. This may lead over time to the accumulation of mutations in the viral genome and, eventually, to the emergence of drug-resistant viruses, which may affect the efficacy of the therapy and the patient’s quality of life. To overcome some of the limitations of the standard antiretroviral therapy, innovative therapeutic approaches such as “shock and kill” and immunotherapies, as well as technologies based on RNA interference and CRISPR-Cas9 genome editing are under investigation. Nevertheless, the virus may find a way to break free even from these novel strategies. In this review, we focus on the mechanisms that enable HIV-1 escape from the most advanced therapies and discuss some of the challenges to prevent this issue

Ebola Virus Entry: From Molecular Characterization to Drug Discovery

Ebola Virus Disease (EVD) is one of the most lethal transmissible infections, characterized by a high fatality rate, and caused by a member of the Filoviridae family. The recent large outbreak of EVD in Western Africa (2013\u207b2016) highlighted the worldwide threat represented by the disease and its impact on global public health and the economy. The development of highly needed anti-Ebola virus antivirals has been so far hampered by the shortage of tools to study their life cycle in vitro, allowing to screen for potential active compounds outside a biosafety level-4 (BSL-4) containment. Importantly, the development of surrogate models to study Ebola virus entry in a BSL-2 setting, such as viral pseudotypes and Ebola virus-like particles, tremendously boosted both our knowledge of the viral life cycle and the identification of promising antiviral compounds interfering with viral entry. In this context, the combination of such surrogate systems with large-scale small molecule compounds and haploid genetic screenings, as well as rational drug design and drug repurposing approaches will prove priceless in our quest for the development of a treatment for EVD

Herpes simplex virus type 2 infection increases human immunodeficiency virus type 1 entry into human primary macrophages

Epidemiological and clinical data indicate that genital ulcer disease (GUD) pathogens are associated with an increased risk of human immunodeficiency virus type 1 (HIV-1) acquisition and/or transmission. Among them, genital herpes simplex virus type 2 (HSV-2) seems to play a relevant role. Indeed, the ability of HSV-2 to induce massive infiltration at the genital level of cells which are potential targets for HIV-1 infection may represent one of the mechanisms involved in this process. Here we show that infection of human primary macrophages (MDMs) by HSV-2 results in an increase of CCR5 expression levels on cell surface and allows higher efficiency of MDMs to support entry of R5 HIV-1 strains. This finding could strengthen, at the molecular level, the evidence linking HSV-2 infection to an increased susceptibility to HIV-1 acquisition

Pandemic influenza A (H1N1v) infection in pediatric population: a multicenter study in a North-East area of Italy

<p>Abstract</p> <p>Background -</p> <p>Data on clinical presentation, morbidity and mortality of 2009 pandemic influenza virus (H1N1v) in paediatric population are still emerging; most of the data so far available came from selected cohorts of children admitted to tertiary care paediatric hospitals.</p> <p>Methods -</p> <p>An observational study involving all the 19 Divisions of Paediatrics of the Veneto Region was conducted with the aim of investigating into the demographic and clinical characteristics, the treatment, the outcome and the risk factors for disease severity of H1N1v infection occurring in children.</p> <p>Results -</p> <p>Two hundred children, median age of 4.15 years (range 0-15) were enrolled from the last week of October till the first week of January 2010 for an overall hospitalization rate of 23/100.000. At least one underlying medical condition was found in 44% of patients. Fever and cough were the most frequent symptoms (93% and 65% respectively). 11 patients (6%) were admitted to a PICU and 5 (2.5%) required mechanical ventilation. Antiviral therapy was administered in 103 patients (51.5%) Death occurred in 2 patients (1%); both had severe prior medical conditions. Pre-existing neurologic diseases (OR 7.82; 95%CI: 1.15-53.34), the presence of hypoxemia (OR 10.47; 95%CI: 2.12-51.70) and anemia (Haemoglobin < 10 g/dL) (OR 14.15; 95%CI: 2.36-84.64) were risk factor for Intensive Care Unit admission.</p> <p>Conclusions -</p> <p>This observational study in a given area of North-East Italy confirms the rather favourable prognosis of children with influenza A H1N1 (2009). Pre-existing conditions, and which is new, significant anemia, are risk factors for a complicated course.</p

Report of two cases of influenza virus A/H1N1v and B co-infection during the 2010/2011 epidemics in the Italian Veneto Region

From October 2010 to April 2011, in the Italian Veneto Region, 1403 hospitalized patients were tested for influenza virus infection by specific real time RT-PCR. Overall, 327 samples were positive for either influenza A (75%) or B (25%) viruses. Among these positive patients two resulted co-infected by A/H1N1v and B viruses. Even though co-infection with both influenza A and B viruses appears to be a rare event, it occurs naturally and may play a role in epidemiology and pathogenicity. In the present study the two co-infected patients were a transplant recipient immunocompromised adult and a child displaying a severe respiratory illness. The co-infection was confirmed by inoculation of the nasopharyngeal swabs in MDCK.2 cells, followed by immunofluorescence and real time RT-PCR assays. Moreover, in the case of the adult patient, the immune system response against both viruses was assayed by hemoagglutination inhibition test against reference influenza virus strains. Both patients fully recovered from infection, without significant differences with mono-infected patients

Amiodarone and metabolite MDEA inhibit Ebola virus infection by interfering with the viral entry process

Ebola virus disease (EVD) is one of the most lethal transmissible infections characterized by a high fatality rate, and a treatment has not been developed yet. Recently, it has been shown that cationic amphiphiles, among them the antiarrhythmic drug amiodarone, inhibit filovirus infection. In the present work, we investigated how amiodarone interferes with Ebola virus infection. Wild-type Sudan ebolavirus and recombinant vesicular stomatitis virus, pseudotyped with the Zaire ebolavirus glycoprotein, were used to gain further insight into the ability of amiodarone to affect Ebola virus infection. We show that amiodarone decreases Ebola virus infection at concentrations close to those found in the sera of patients treated for arrhythmias. The drug acts by interfering with the fusion of the viral envelope with the endosomal membrane. We also show that MDEA, the main amiodarone metabolite, contributes to the antiviral activity. Finally, studies with amiodarone analogues indicate that the antiviral activity is correlated with drug ability to accumulate into and interfere with the endocytic pathway. Considering that it is well tolerated, especially in the acute setting, amiodarone appears to deserve consideration for clinical use in EV

Zoonoses Surveillance in Italy (2000-2009): Investigation on Animals with Neurological Symptoms

Zoonoses are defined by the World Health Organization (WHO) as \u201cThose diseases and infections naturally transmitted between vertebrae animals and man\u201d (WHO 1959) (Palmer et al., 1998). They may be caused by viruses, bacteria, including chlamidiae and rickettsiae, fungi, protozoa, helminths and arthropods (Krauss et al., 2003), and transmitted directly (through contact with skin, hair, eggs, blood or secretions) or indirectly (by insect vectors and ingestion of contaminated food). Currently, 1415 pathogens for humans have been identified and of these approximately 61% (868) are agents of zoonoses, some of which manifest with neurological signs; 132 agents are also associated with emerging zoonoses (Asjo et al., 2007; Matassa, 2007; Taylor et al. , 2001). Neurological zoonoses are widespread, especially in the developing countries where they are not even diagnosed in most cases. Emerging zoonoses of recently identified pathogens are Lyme disease, cryptosporidiosis, West Nile disease, transmissible spongiform encephalopathy, and possible variants of the avian influenza virus, which have found new favourable conditions for spreading. In contrast, re-emerging zoonoses are well-known diseases considered as eradicated in a given country but recur with an exponentially increasing incidence, such as tuberculosis, leptospirosis, rabies (Matassa, 2007)