Publications by authors named "Alessandra Scagliarini"

51 Publications

VEGF-R2/Caveolin-1 Pathway of Undifferentiated ARPE-19 Retina Cells: A Potential Target as Anti-VEGF-A Therapy in Wet AMD by Resvega, an Omega-3/Polyphenol Combination.

Int J Mol Sci 2021 Jun 19;22(12). Epub 2021 Jun 19.

Université de Bourgogne Franche-Comté, 21000 Dijon, France.

Age-related macular degeneration (AMD) is one of the main causes of deterioration in vision in adults aged 55 and older. In spite of therapies, the progression of the disease is often observed without reverse vision quality. In the present study, we explored whether, in undifferentiated ARPE-19 retinal cells, a disruption of the VEGF receptors (VEGF-R)/caveolin-1 (Cav-1)/protein kinases pathway could be a target for counteracting VEGF secretion. We highlight that Resvega, a combination of omega-3 fatty acids with an antioxidant, resveratrol, inhibits VEGF-A secretion in vitro by disrupting the dissociation of the VEGF-R2/Cav-1 complex into rafts and subsequently preventing MAPK activation. Moreover, DNA ChIP analysis reveals that this combination prevents the interaction between AP-1 and and gene promoters. By these pathways, Resvega could present a potential interest as nutritional complementation against AMD.
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http://dx.doi.org/10.3390/ijms22126590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234996PMC
June 2021

Natural distemper infection in stone martens (Martes foina): From infection to neutralizing antibodies.

Res Vet Sci 2021 Sep 18;138:196-200. Epub 2021 Jun 18.

Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Via Tolara di Sopra 50, Ozzano Emilia, BO 40064, Italy. Electronic address:

We report an outbreak of canine distemper virus (CDV) among stone martens (Martes foina) in Italy. After being rescued in Northern Italy between April and June 2018, six subjects were kept in a wildlife and exotic animal rescue center in Bologna province. Subjects have been monitored for 15 months in captivity. Within this time-lapse, two subjects died, while among the remaining four, only one showed clinical symptoms referable to distemper. Surviving subjects have been regularly tested for CDV by means of reverse transcriptase-PCR from conjunctival and oropharyngeal swabs for eleven months. The identified viruses belonged to the Wildlife-Europe CDV genetic subgroup. Neutralizing antibodies were detected at the end of the eleven months, when all subjects tested reverse transcriptase-PCR negative. Our findings confirm the circulation of the Wildlife-Europe CDV genetic subgroup (Europe 1/South America 1 lineage) within the Italian wildlife, and improve knowledge on viral infection in stone martens.
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http://dx.doi.org/10.1016/j.rvsc.2021.06.015DOI Listing
September 2021

Epidemiologic case investigation on the zoonotic transmission of Staphylococcus aureus infection from goat to veterinarians.

Zoonoses Public Health 2021 May 5. Epub 2021 May 5.

Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.

Staphylococcus aureus infection led to a case of goat abortion, and four veterinarians contracted S. aureus infection from the goat during and after the abortion. Three veterinarians assisted a doe during the dystocic delivery of a dead foetus. Seventy-two hours after the dystocia, which ended with the goat's death, the veterinarians who assisted during the kidding and the veterinarian who performed the necropsy showed the presence of multiple, isolated, painful pustules 1-5 mm in diameter located along their forearms and knees. S. aureus was isolated from the pustules of the veterinarians, the placenta and uterus of the goat, the organs (brain, thymus gland, abomasum, liver and spleen) of the foetus, the scrotum and eye swabs of the buck, and mammary pustules of another goat from the same herd. Histological analysis revealed purulent metritis and inflammation of the placental cotyledons. Additional investigations eliminated the chances of other infections. S. aureus isolates recovered from the veterinarians, goats, foetus and buck were sensitive to the tested anti-microbials and did not encode staphylococcal enterotoxin genes (sea, ser, sep, see, seg and sei). The isolates were closely related, as indicated by the results of Fourier-transform infrared spectroscopy and comparative whole-genome sequencing analysis. The results of this study clearly support the hypothesis that an episode of professional zoonosis was caused by S. aureus infection during the abortion and also highlight the need for bacterial subtyping in epidemiological surveys.
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http://dx.doi.org/10.1111/zph.12836DOI Listing
May 2021

Bovine viral diarrhoea virus 1b infection associated with congenital tremor and hypomyelination in Holstein calves.

Vet Microbiol 2021 May 23;256:109047. Epub 2021 Mar 23.

Department of Veterinary Medical Sciences, University of Bologna, via Tolara di Sopra 50, 40064, Ozzano Emilia, Italy. Electronic address:

Hypomyelination is a rare consequence of in utero bovine viral diarrhoea virus (BVDV) infection. We describe a BVDV outbreak in a naïve Holstein dairy herd in northern Italy, with an unusually high prevalence of calves with neurological signs, generalised tremors and ataxia. Histological analysis showed that hypomyelination was the predominant lesion and that the most typical BVDV neuropathological findings (e.g. cerebellar hypoplasia) were absent. Virological and molecular analyses showed that non-cytopathic BVDV genotype 1b was associated with the calves' neurological signs and excluded other viruses responsible for congenital infection or neurological disorders. Whole-genome sequencing of BVDVs from the brain of a calf with neurological signs and the whole blood of a persistently infected herd-mate with no such sign showed >99.7 % sequence identity. Analysis of the quasispecies distribution revealed the greatest variation rates in regions coding for the structural proteins E1 and E2. Variation was slightly greater in the brain- than in the blood-derived sequence and occurred at different sites, suggesting the occurrence of distinct evolutionary processes in the two persistently infected calves. Molecular characterisation of BVDV genomes from five other calves with neurological signs from the same farm confirmed that the E1 and E2 regions were the most variable. Several factors, including genetic variability and host factors, appear to have contributed to the observed unique BVDV disease phenotype, characterised by hypomyelination and neurological signs.
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http://dx.doi.org/10.1016/j.vetmic.2021.109047DOI Listing
May 2021

Bovine Papillomatosis Hiding a Zoonotic Infection: Epitheliotropic Viruses in Bovine Skin Lesions.

Pathogens 2020 Jul 17;9(7). Epub 2020 Jul 17.

Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "Bruno Ubertini" (IZSLER), 25124 Brescia, Italy.

We describe two cases of skin co-infections with epitheliotropic viruses, detected in two cattle during lumpy skin disease (LSD) surveillance in northern Italy. A diagnostic protocol including different molecular methods as well as negative staining electron microscopy was applied to detect the most common viral agents belonging to the family , and which cause skin diseases in cattle. Two specimens were collected from cases clinically diagnosed as papillomatosis and pseudo-LSD. Both skin lesions were shown to harbor more than one viral species. This case report shows, for the first time, co-infection of zoonotic parapoxvirus with bovine papillomavirus and herpesvirus in skin lesions of cattle. In particular, the simultaneous presence of virions morphologically referable to parapoxvirus and papillomavirus confirms that the replication of both viruses in the same lesion can happen and the so-called papillomatosis can bear zoonotic viruses.
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http://dx.doi.org/10.3390/pathogens9070583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400346PMC
July 2020

COVID-19: An Appeal for an Intersectoral Approach to Tackle With the Emergency.

Front Public Health 2020 16;8:302. Epub 2020 Jun 16.

Department of Veterinary Medicine, Mediterranean Center for Disease Control (MCDC), University of Sassari, Sassari, Italy.

The knowledge of disease determinants is a pre-requisite for disease prevention. Infectious diseases determinants can be classified in three ways, as: primary or secondary; intrinsic or extrinsic; and associated with host, agent, or environment. In the specific case of COVID-19 several of these determinants are currently unknown leading to difficulties in public health approach to this disease. In this paper, we attempt to address several of the current gaps on COVID-19 using a systematic analysis on recent findings and some preliminary knowledge on animal coronaviruses. A discussion on the impact of COVID-19 determinants in disease prevention and control will be based on the Environmental Change and Infectious Disease (EnVID) systemic framework to address several challenges that may affect the control of the SARS- CoV-2 pandemic spread both in industrialized and in developing Countries.
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http://dx.doi.org/10.3389/fpubh.2020.00302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308477PMC
May 2021

Bovine Papillomavirus 1 Gets Out of the Flock: Detection in an Ovine Wart in Sicily.

Pathogens 2020 May 30;9(6). Epub 2020 May 30.

Dipartimento di Scienze Mediche Veterinarie, Università di Bologna, Ozzano Emilia, 40064 Bologna, Italy.

A proliferative cauliflower lesion was excised from the udder of a sheep. Histological investigation confirmed the macroscopic classification of the lesion as a papilloma, without any fibroblastic proliferation. PCR revealed the presence of bovine papillomavirus (BPV), which was further confirmed by the identification of a by Next Generation Sequencing analysis. This was subsequently classified as bovine papillomavirus type 1. Negative staining electron microscopy (EM) analyses produced negative test results for papillomavirus particles. RNA in situ hybridization (ISH) confirmed the presence of BPV-1. The results further confirm the ability of BPVs belonging to the genus to infect distantly related species and to cause lesions that are different from sarcoids.
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http://dx.doi.org/10.3390/pathogens9060429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350338PMC
May 2020

Epitheliotropic Infections in Wildlife Ruminants From the Central Alps and Stelvio National Park.

Front Vet Sci 2020 30;7:229. Epub 2020 Apr 30.

Dipartimento di Medicina Specialistica Diagnostica e Sperimentale, Alma Mater Studiorum, Università di Bologna, Bologna, Italy.

The mountain chain of the Alps, represents the habitat of alpine fauna where the red deer () population is the outmost numerous, followed by the chamois () and the alpine ibex () at higher altitudes. Previous reports showed the circulation of epitheliotropic viruses, belonging to the families and , causing skin and mucosal lesions in wild ruminants of the Stelvio National Park, situated in the area. To deepen our knowledge on the natural dynamics of the infections, a passive surveillance on all the cases of proliferative skin and mucosal lesions in wild ruminants was performed. Twenty-seven samples (11 chamois, 10 red deer and 6 ibex) collected from 2008 to 2018 were analyzed by negative staining electron microscopy, histology, and PCR followed by genome sequencing and phylogenetic analyses. Results confirmed the spread of Parapoxvirus of Red Deer in New Zealand (PVNZ) in Italy, and its ability to cause severe lesions i.e., erosions and ulcers in the mouth. We showed for the first time a PVNZ/CePV1v (C papillomavirus 1 variant) co-infection identified in one red deer. This result supports previous evidence on the ability of papillomavirus and parapoxvirus to mutually infect the same host tissue. Interestingly two ibex and one chamois showing orf virus (OV) skin lesions were shown to be co-infected with bovine papillomavirus type 1 and 2. The presence of bovine papillomavirus, in orf virus induced lesions of chamois and ibex raises the question of its pathogenetic role in these animal species. For the first time, OV/CePV1v co-infection was demonstrated in another chamois. CePV1v is sporadically reported in red deer throughout Europe and is considered species specific, its identification in a chamois suggests its ability of cross-infecting different animal species. Poxviruses and papillomavirus have been simultaneously detected also in the skin lesions of cattle, bird and human suggesting a possible advantageous interaction between these viruses. Taken together, our findings add further information on the epidemiology and pathogenetic role of epitheliotropic viruses in wild ruminants living in the central Alps and in Stelvio National Park.
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http://dx.doi.org/10.3389/fvets.2020.00229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203578PMC
April 2020

Xanthohumol, a Prenylated Flavonoid from Hops, Induces DNA Damages in Colorectal Cancer Cells and Sensitizes SW480 Cells to the SN38 Chemotherapeutic Agent.

Cells 2020 04 10;9(4). Epub 2020 Apr 10.

Université de Bourgogne Franche-Comté, F-21000 Dijon, France.

In spite of chemotherapy and systematic screening for people at risk, the mortality rate of colorectal cancer (CRC) remains consistently high, with 600,000 deaths per year. This low success rate in the treatment of CRC results from many failures associated with high resistance and the risk of metastasis. Therefore, in response to these therapeutic failures, new strategies have been under development for several years aimed at increasing the effect of anticancer compounds and/or at reducing their secondary effects on normal cells, thus enabling the host to better withstand chemotherapy. This study highlights that xanthohumol (Xn) concentrations under the IC values were able to induce apoptosis and to enhance the DNA-damage response (DDR). We demonstrate for the first time that Xn exerts its anticancer activity in models of colon cancer through activation of the ataxia telangiectasia mutated (ATM) pathway. Subsequently, the ability of Xn to restore DNA damage in CRC cells can sensitize them to anticancer agents such as SN38 (7-ethyl-10-hydroxycamptothecin) used in chemotherapy.
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http://dx.doi.org/10.3390/cells9040932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226974PMC
April 2020

Cutaneous Fibropapilloma in a Red Deer () Associated with Papillomavirus in Portugal.

J Wildl Dis 2020 07 9;56(3):636-639. Epub 2020 Jan 9.

Department of Veterinary Medical Sciences, Alma Mater Studiorum University of Bologna, Italy.

A pedunculated cauliflower-like mass was detected on the left posterior limb of a subadult male red deer () after a hunt in Portugal. Histologically the lesion was classified as cutaneous fibropapilloma. The identification of papillomavirus (CePV-1 variant) was based on sequencing of the L1 gene. The L2 sequence revealed a nine-nucleotide deletion, as already reported in the Italian and Hungarian CePV-1, further supporting the theory that this is a distinctive genomic characteristic of this viral variant, as this feature has been found in distinct cases from geographically distant countries. In addition, a coinfection with bovine papillomavirus was evidenced by amplification and sequencing of the E5 gene, confirming the ability of Delta papillomaviruses to cross-infect different animal species and providing more evidence that wildlife may act as reservoir for papillomaviruses affecting domestic species. Papillomavirus infection in red deer has been sporadically described in different European countries; in this work, we describe the identification of a CePV-1 variant infection associated with a red deer fibropapilloma in Portugal.
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http://dx.doi.org/10.7589/2019-03-070DOI Listing
July 2020

Molecular Detection of Bovine Papillomavirus DNA in the Placenta and Blood of Healthy Mares and Respective Foals.

Vet Sci 2019 Feb 6;6(1). Epub 2019 Feb 6.

Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50 Ozzano Emilia, Bologna 40064, Italy.

Despite the characteristic species specificity of Papillomaviruses (PVs), the bovine papillomavirus (BPV) types 1, 2, and-more rarely-13, can cross-infect equids, where they are involved in the pathogenesis of sarcoid neoplasms. Sarcoids are locally invasive fibroblastic skin tumors that represent the most common skin neoplasms in horses worldwide. The transmission mechanism of BPV is still controversial in horses. Thus far, direct and indirect routes have been implicated, while vertical transmission has been suggested after the detection of viral DNA in the semen of healthy stallions. Testing of the blood and placenta of non-sarcoid baring mares and their respective foals revealed that the equine placenta can harbor BPV DNA, leading us to speculate a possible prenatal vertical DNA transmission in equids.
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http://dx.doi.org/10.3390/vetsci6010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466198PMC
February 2019

Tumor-derived granzyme B-expressing neutrophils acquire antitumor potential after lipid A treatment.

Oncotarget 2018 Jun 19;9(47):28364-28378. Epub 2018 Jun 19.

Laboratoire d'Immunologie et Immunothérapie des Cancers, EPHE, PSL Research University, 75000 Paris, France.

Neutrophils are known to possess both pro- and anti-tumor properties, a feature that could be related to the diversity and plasticity of these cells. Here we explored the hypothesis that under an appropriate environment and stimuli, neutrophils could induce an effective response against tumor cells. In a rat and mouse models, we show that a substantial amount of colon tumor associated-neutrophils (TAN) expressed the cytolytic enzyme granzyme B, which is absent in spleen or blood circulating neutrophils. This TAN population was also found into tumors of patients with colon cancer. Tumor neutrophil infiltration was correlated with an increase of chemokines known to attract neutrophils in both rat models and patients. These cells were involved in a Lipid A analog-mediated colon tumor regression. Mechanistically, treating the rats with the Lipid A analog triggered granzyme B release from neutrophils in tumor cell vicinity, which was correlated to tumor regression. Alteration of granzyme B function in tumor cells decreased the cytotoxic effect of Lipid A in rat and mouse models. Granzyme B expression in neutrophils could be induced by the lipid A analog but also by some of the cytokines that were detected in the tumor microenvironment. These results identify a subpopulation of neutrophils expressing granzyme B that can act as a key player of lipid A-mediated colon cancer regression in rat and mouse models and the molecular mechanisms involved may provide novel approaches for human therapeutic intervention.
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http://dx.doi.org/10.18632/oncotarget.25342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033356PMC
June 2018

Case report of a pustular dermatitis outbreak in sheep: Clinical and food safety considerations.

Ital J Food Saf 2018 Mar 11;7(1):6980. Epub 2018 Apr 11.

Department of Veterinary Medical Sciences, University of Bologna.

The objective of this report is to describe an outbreak of pustular dermatitis in a flock of about 200 sheep, its clinical evolution and food safety implications. The onset of the symptoms was sudden and the lesions spread very quickly from ewe to ewe, so that in about 3 days almost all of the lactating sheep were stricken. Pustules from 5 different animals, six milk samples, two cheese samples, teat cup samples from the milking machine and farmer's hands were analysed. A pure culture of , producing staphylococcal enterotoxin (SE) C, was isolated from pustules. Milk and cheese showed a contamination by coagulase positive staphylococci <15 and 30 colony forming units respectively and the absence of SE. Farmer's hands and teat cups samples resulted negative for coagulase positive staphylococci. Therapy with daily topical medicaments was prescribed and a prophylactic intervention was suggested by the administration of an autovaccine. The low level of milk and cheese contamination and the absence of SE in cheese supported the decision to not advise the farmer to recall cheese produced with milk from affected animals.
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http://dx.doi.org/10.4081/ijfs.2018.6980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5913706PMC
March 2018

In vivo nose-to-brain delivery of the hydrophilic antiviral ribavirin by microparticle agglomerates.

Drug Deliv 2018 Nov;25(1):376-387

b Department of Food and Drug , University of Parma , Parma , Italy.

Nasal administration has been proposed as a potential approach for the delivery of drugs to the central nervous system. Ribavirin (RBV), an antiviral drug potentially useful to treat viral infections both in humans and animals, has been previously demonstrated to attain several brain compartments after nasal administration. Here, a powder formulation in the form of agglomerates comprising micronized RBV and spray-dried microparticles containing excipients with potential absorption enhancing properties, i.e. mannitol, chitosan, and α-cyclodextrin, was developed for nasal insufflation. The agglomerates were characterized for particle size, agglomeration yield, and ex vivo RBV permeation across rabbit nasal mucosa as well as delivery from an animal dry powder insufflator device. Interestingly, permeation enhancers such as chitosan and mannitol showed a lower amount of RBV permeating across the excised nasal tissue, whereas α-cyclodextrin proved to outperform the other formulations and to match the highly soluble micronized RBV powder taken as a reference. In vivo nasal administration to rats of the agglomerates containing α-cyclodextrin showed an overall higher accumulation of RBV in all the brain compartments analyzed as compared with the micronized RBV administered as such without excipient microparticles. Hence, powder agglomerates are a valuable approach to obtain a nasal formulation potentially attaining nose-to-brain delivery of drugs with minimal processing of the APIs and improvement of the technological and biopharmaceutical properties of micronized API and excipients, as they combine optimal flow properties for handling and dosing, suitable particle size for nasal deposition, high surface area for drug dissolution, and penetration enhancing properties from excipients such as cyclodextrins.
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http://dx.doi.org/10.1080/10717544.2018.1428242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6058489PMC
November 2018

Lysophosphatidylcholine acyltransferase 2-mediated lipid droplet production supports colorectal cancer chemoresistance.

Nat Commun 2018 01 22;9(1):322. Epub 2018 Jan 22.

University of Bourgogne-Franche Comté, F-21000, Dijon, France.

Lipid droplet (LD) accumulation is a now well-recognised hallmark of cancer. However, the significance of LD accumulation in colorectal cancer (CRC) biology is incompletely understood under chemotherapeutic conditions. Since drug resistance is a major obstacle to treatment success, we sought to determine the contribution of LD accumulation to chemotherapy resistance in CRC. Here we show that LD content of CRC cells positively correlates with the expression of lysophosphatidylcholine acyltransferase 2 (LPCAT2), an LD-localised enzyme supporting phosphatidylcholine synthesis. We also demonstrate that LD accumulation drives cell-death resistance to 5-fluorouracil and oxaliplatin treatments both in vitro and in vivo. Mechanistically, LD accumulation impairs caspase cascade activation and ER stress responses. Notably, droplet accumulation is associated with a reduction in immunogenic cell death and CD8 T cell infiltration in mouse tumour grafts and metastatic tumours of CRC patients. Collectively our findings highlight LPCAT2-mediated LD accumulation as a druggable mechanism to restore CRC cell sensitivity.
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http://dx.doi.org/10.1038/s41467-017-02732-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778070PMC
January 2018

Host cell tropism, genome characterization, and evolutionary features of OaPV4, a novel Deltapapillomavirus identified in sheep fibropapilloma.

Vet Microbiol 2017 May 27;204:151-158. Epub 2017 Apr 27.

Dipartimento di Medicina Veterinaria dell'Università degli Studi di Sassari, Via Vienna 2, 07100 Sassari, Italy. Electronic address:

Investigating papillomavirus (PV) diversity is crucial to fully comprehend pathogenicity, genetic features, and evolution of taxa hosted by domestic and wild animal species. This study reports the identification of OaPV4, a novel ovine PV type within Deltapapillomaviruses 3. The study of OaPV4 genomic features combined to in situ hybridization and immunohistochemistry investigations allowed extrapolating several general biological features of ovine PVs, such as their cellular tropism, pathogenicity, and evolutionary history. Based on results, ovine PVs can be grouped into a polyphyletic ancient group of viruses, which splits in two main subgroups having peculiar cellular tropism and pathogenicity. Results add up to animal PV diversity and are crucial to future studies aimed to investigate the correlation between animal PV and cutaneous benign and malign proliferations.
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http://dx.doi.org/10.1016/j.vetmic.2017.04.024DOI Listing
May 2017

Multiple gene typing and phylogeny of avipoxvirus associated with cutaneous lesions in a stone curlew.

Vet Res Commun 2017 Jun 4;41(2):77-83. Epub 2017 Jan 4.

Department of Veterinary Medicine, University of Sassari, Via Vienna 2, 07100, Sassari, Italy.

Avipoxvirus (APV) infections have been observed in a wide variety of wild, captive and domestic avian hosts, recently including a range of island endemic and endangered species. However, not enough is known about genome diversity and phylogenetic relationships of APVs, as well as their host-range specificity. A wild stone curlew (Burhinus oedicnemus) was recovered in Sardinia (Italy), showing large wart-like lesions and nodules on both legs and toes, which resulted positive to poxvirus by PCR. Histopathological examination of the lesions showed ballooning degeneration and large intracytoplasmic inclusion bodies consistent with APV infection. A multiple gene sequencing approach was applied to highlight the phylogenetic relationships of this virus with a panel of selected APVs at the clade and subclade levels. This novel isolate was characterized by sequencing partial 4b core protein, P35 (locus fpv140) and DNA polymerase genes and phylogenetic analyses assigned it to clade A, (Fowlpox virus, FWPV), subclade A2. Conservation implications of avian pox presence in Sardinian stone curlews and possibly in other island bird species are discussed.
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http://dx.doi.org/10.1007/s11259-016-9674-5DOI Listing
June 2017

p16 Immunostaining of Canine Squamous Cell Carcinomas Is Not Associated with Papillomaviral DNA.

PLoS One 2016 21;11(7):e0159687. Epub 2016 Jul 21.

Pathology Division, Department of Veterinary Medical Sciences, University of Bologna, Ozzano Emilia (BO), Italy.

While papillomavirus (PVs) are an established cause of human cancer, few reports have supported a relationship between PV and canine squamous cell carcinomas (SCCs). Human oncogenic PVs lead to an increased expression of the p16 tumor suppressor protein, and the latter can be demonstrated immunohistochemically to support a likely causal relationship between tumor and PV infection. In the present study, archive samples of canine SCC from different anatomical locations were tested by polymerase chain reaction for the presence of PV DNA and by p16 immunohistochemistry. The aims were to investigate the relationship between p16 expression and presence of PV DNA, in order to assess the utility of p16 overexpression as a biomarker of PV infection in canine SCC. A total of 52 SCCs were included. Nine cases (17.3%) showed moderate p16 immunoreactivity, with no association with tumor degree of differentiation, histotype or mitotic activity. The canPVf/FAP64 primers amplified Canis familiaris PV-1 DNA from 3 out of 52 tumors (5.8%), one cutaneous, one oral and one tonsillar SCC. There was no association between PV presence and p16 immunostaining. These results do not support a significant role of PVs in the development of canine SCCs. Additionally, PV infection was apparently not the cause of the p16 immunostaining observed in a subset of canine SCCs. A better awareness of p16 level of expression and cellular function in canine cancer may help to define its diagnostic and prognostic role.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159687PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956233PMC
July 2017

Identification and Characterization of Fringilla coelebs Papillomavirus 1 (FcPV1) in Free-living and Captive Birds in Italy.

J Wildl Dis 2016 07 20;52(3):756-8. Epub 2016 Jun 20.

1 Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "Bruno Ubertini," Via Bianchi 9, 25124 Brescia, Italy;

A papillomavirus (PV) was identified by negative-staining electron microscopy in skin lesions of two bird species (Fringillidae) in Italy. Genetic analyses revealed an FcPV1 with a low genetic variability in the E6, E7, E1, E2, and L1 genes and the long control region when compared to the FcPV1 reference strain.
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http://dx.doi.org/10.7589/2015-09-254DOI Listing
July 2016

Bovine papillomavirus type 7 in Italy: complete genomes and sequence variants.

Virus Genes 2016 Apr 2;52(2):253-60. Epub 2016 Feb 2.

Department of Veterinary Medical Sciences, Alma Mater Studiorum, University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano Emilia, Bologna, Italy.

Two novel bovine papillomavirus type 7 (BPV-7) variants have been identified in teat cutaneous papillomas affecting dairy cows in northern Italy. The entire genome sequences of two BPV-7 Italian variants showed major sequence differences in the long control region (LCR) and in the L2 gene compared to the Japanese reference strain. In order to define the stability of these genetic variants, the L2 and LCR sequences of seven further BPV-7 positive isolates were characterized. An insertion of six amino acids in the L2 structural protein has been detected in all samples while different genetic variants have been identified for the LCR. These findings provide new insights on intra-type variability of BPVs and represent a starting point for future studies aimed at establishing the biological role of the different BPV genomic regions and investigating the pathogenic potential of papillomavirus variants.
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http://dx.doi.org/10.1007/s11262-016-1298-xDOI Listing
April 2016

Evidence of zoonotic Poxviridae coinfections in clinically diagnosed papillomas using a newly developed mini-array test.

J Vet Diagn Invest 2016 Jan 23;28(1):59-64. Epub 2015 Dec 23.

Department of Veterinary Medical Sciences, Alma Mater Studiorum, Università di Bologna, Ozzano dell'Emilia, Bologna, Italy (Scagliarini, Casà, Gallina, Savini)Acobiom, Biopôle Euromédecine II, Montpellier Cedex 4, France (Trentin, Morent, Piquemal)Department of Virology, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna "Bruno Ubertini", Brescia, Italy (Lavazza)Istituto Zooprofilattico Sperimentale della Sicilia, Palermo, Italy (Puleio, Buttaci, Cannella, Purpari, Di Marco, Guercio).

Our study describes a newly developed mini-array test for the rapid detection of poxviruses in animals and humans. The method is based on detection that combines target nucleic acid amplification by polymerase chain reaction and specific hybridization, using enzyme-linked antibodies, allowing identification of zoonotic orthopoxviruses and parapoxviruses in animal and human biological samples. With 100% specificity, the test rules out the possibility of cross-reactions with viral agents causing look-alike diseases. The assay was employed in the field to investigate the causes of several outbreaks of a malignant proliferative skin disease that affected domestic ruminants in Sicily during 2011-2014. Due to specific aspects of the lesions, the animals were clinically diagnosed with papillomatosis. The mini-array test allowed the identification of coinfections caused by more than 1 viral species belonging to the Parapoxvirus and Orthopoxvirus genera, either in goats or in cattle. Our study suggests that the so-called "papillomatosis" can be the result of multiple infections with epitheliotropic viruses, including zoonotic poxviruses that cannot be properly identified with classical diagnostic techniques.
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http://dx.doi.org/10.1177/1040638715614604DOI Listing
January 2016

PAPILLOMAVIRUS IN HEALTHY SKIN AND MUCOSA OF WILD RUMINANTS IN THE ITALIAN ALPS.

J Wildl Dis 2016 Jan 5;52(1):82-7. Epub 2015 Nov 5.

1  Department of Veterinary Medical Sciences, Alma Mater Studiorum, University of Bologna, Via Tolara di sopra 50, 40064 Ozzano Emilia, Bologna, Italy.

We investigated healthy skin and mucosal specimens of wild ruminants in the Italian Alps. We identified bovine papillomavirus (BPV)-2 DNA in the healthy skin of wild ruminants and documented coinfection of BPV-1 and Cervus elaphus papillomavirus (CePV)-1 in a healthy red deer (Cervus elaphus). We also demonstrated cross-infections of BPVs of the genus Xipapillomavirus, both as single virus infection and also in association with Deltapapillomavirus types 1 and 2, confirming that host tropism of papillomaviruses is not as species-specific as previously thought. Our results suggest that subclinical infections could be linked to the presence of domestic ruminants sharing the same habitat with wild species and that the wildlife may act as a reservoir for papillomaviruses affecting domestic species.
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http://dx.doi.org/10.7589/2015-03-065DOI Listing
January 2016

E5 nucleotide polymorphisms suggest quasispecies occurrence in BPV-1 sub-clinically infected horses.

Res Vet Sci 2015 Oct 31;102:80-2. Epub 2015 Jul 31.

Department of Veterinary Medical Sciences-Alma Mater Studiorum - University of Bologna, Via Tolara di sopra 50, 40064 Ozzano Emilia, Bologna, Italy. Electronic address:

BPV-1 is known as the main causative agent of equine sarcoid, but the virus has also been detected in skin and blood of healthy horses. Previous reports demonstrated the presence of E5 variants in sarcoids of donkeys and horses; we investigated whether this genetic variability might be also found in BPV-1, PBMC associated, of sub-clinically infected horses. With this aim, we analyzed the E5 gene of 21 BPV-1 strains from diseased and sub-clinically infected horses. Our analyses lead us to demonstrate that multiple sequence variants can be present in the blood of sub-clinically infected horses, with alternative bases corresponding to either synonymous or non-synonymous codons in the E5 oncogene sequences. The results give support to the proposed existence of "equine adapted" BPV-1 strains with the occurrence of viral variants, resembling quasispecies, in clinically healthy horses with viremia.
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http://dx.doi.org/10.1016/j.rvsc.2015.07.016DOI Listing
October 2015

Senescence of tumor cells induced by oxaliplatin increases the efficiency of a lipid A immunotherapy via the recruitment of neutrophils.

Oncotarget 2014 Nov;5(22):11442-51

EPHE Cancer Immunotherapy Laboratory, EA7269 EPHE-University of burgundy, Dijon, F-21000, France.

Management of advanced colorectal cancer is challenging due to the lack of efficient therapy. The lipid A, OM-174 exhibited antitumor activity in colorectal cancer. We explored the anticancer efficacy of this compound in rats bearing large colorectal tumors in combination with the platinum derivative drugs oxaliplatin and cisplatin. While each drug used alone exhibited partial antitumor activity, sequential treatment with oxaliplatin or cisplatin for one week followed by lipid A injections induced a great regression of colorectal tumors, with more than 95% of rats cured from their tumors. This potent antitumor efficacy of the combined treatments was correlated to the sequential induction of cellular senescence by oxaliplatin, and of apoptosis, mainly triggered by the lipid A. Moreover, a recruitment of tumor-associated neutrophils with N1 phenotype as attested by the expression of inducible nitric oxide synthase was observed with combination of oxaliplatin and lipid A. Neutrophil recruitment within tumor microenvironment was due to oxaliplatin and lipid A-dependent release of neutrophil specific chemoattractants such as cxcl1 and 2. However the N1 phenotype is only dependent of lipid A treatment. These results suggest that the combination of chemotherapy with an immunotherapy is a promising approach to treat patients with advanced colorectal cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294335PMC
http://dx.doi.org/10.18632/oncotarget.2556DOI Listing
November 2014

Occurrence of different Canine distemper virus lineages in Italian dogs.

Vet Ital 2014 Jul-Sep;50(3):227-31

Department of Veterinary Medical Sciences, Alma Mater Studiorum-University of Bologna, Via Tolara di Sopra 50, 40064, Ozzano dell'Emilia (BO), Italy.

This study describes the sequence analysis of the H gene of 7 Canine distemper virus (CDV) strains identified in dogs in Italy between years 2002-2012. The phylogenetic analysis showed that the CDV strains belonged to 2 clusters: 6 viruses were identified as Arctic-like lineage and 1 as Europe 1 lineage. These data show a considerable prevalence of Arctic-like-CDVs in the analysed dogs. The dogs and the 3 viruses more recently identified showed 4 distinctive amino acid mutations compared to all other Arctic CDVs.
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http://dx.doi.org/10.12834/VetIt.52.2173.2DOI Listing
June 2015

A role for peroxisome proliferator-activated receptor gamma in resveratrol-induced colon cancer cell apoptosis.

Mol Nutr Food Res 2014 Sep 30;58(9):1785-94. Epub 2014 Jun 30.

Université de Bourgogne, Dijon, France; Centre de Recherche INSERM U866 - Equipe Chimiothérapie, Métabolisme Lipidique et Réponse Immunitaire Antitumorale, Dijon, France.

Scope: Resveratrol may function as a chemopreventive agent. A recent clinical study demonstrates a reduction in tumor cell proliferation in colorectal patients receiving repeated oral ingestion of resveratrol. However, gaps remain in our knowledge of the molecular mechanisms by which resveratrol exerts its chemopreventive effect. We have previously demonstrated that resveratrol induces apoptosis in colon cancer cells and that resveratrol can sensitize chemoresistant colon cancer cells to various drugs. Based on its ability to activate peroxisome proliferator-activated receptor gamma (PPARγ) in colon cancer cells, we sought to determine the implication of this nuclear transcription factor in resveratrol-induced apoptosis.

Methods And Results: Transient transfection of cancer cells with a dominant-negative PPARγ mutant or treatment with a PPARγ antagonist (GW9662) reversed the inhibitory effect of resveratrol. Moreover, GW9662 prevented disruption of the cell cycle induced by resveratrol and consequently abrogated resveratrol-induced apoptosis. Tumor cell death was potentiated by combining resveratrol with rosiglitazone, a PPARγ agonist.

Conclusion: The results show that PPARγ plays a role in resveratrol-induced apoptosis of colon carcinoma cells. The combination of resveratrol with a PPARγ agonist could be a promising pharmacological approach for treatment of colorectal cancer.
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http://dx.doi.org/10.1002/mnfr.201300962DOI Listing
September 2014

Importance of lipid microdomains, rafts, in absorption, delivery, and biological effects of resveratrol.

Ann N Y Acad Sci 2013 Jul;1290:90-7

University of Burgundy, Dijon, France.

The preventive effects of the phytoalexin trans-resveratrol toward cancer have been largely described at the cellular and molecular levels in both in vivo and in vitro models; however, its primary targets are still poorly identified. In this review, we show the crucial role of cell membrane microdomains, that is, lipid rafts, not solely in the initiation of the early biochemical events triggered by resveratrol leading to cancer cell death, but also in resveratrol absorption and distribution. Resveratrol accumulates in lipid rafts and is then taken up by cells through raft-dependent endocytosis. These events allow early activation of kinase pathways and redistribution of cell death receptors within lipid microdomains, events ultimately leading to apoptotic cell death.
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http://dx.doi.org/10.1111/nyas.12177DOI Listing
July 2013

Development and use of a polarized equine upper respiratory tract mucosal explant system to study the early phase of pathogenesis of a European strain of equine arteritis virus.

Vet Res 2013 Mar 28;44:22. Epub 2013 Mar 28.

Laboratory of Virology, Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke B-9820, Belgium.

The upper respiratory tract mucosa represents the first line of defense, which has to be overcome by pathogens before invading the host. Considering the economic and ethical aspects involved in using experimental animals for pathogenesis studies, respiratory mucosal explants, in which the tissue's three-dimensional architecture is preserved, may be ideal alternatives. Different respiratory mucosal explant cultures have been developed. However, none of them could be inoculated with pathogens solely at the epithelium side. In the present study, equine nasal and nasopharyngeal explants were embedded in agarose (3%), leaving the epithelium side exposed to allow apical inoculation. Morphometric analysis did not show degenerative changes during 72 h of cultivation. The number of apoptotic cells in the mucosa slightly increased over time. After validation, the system was used for apical infection with a European strain (08P178) of equine arteritis virus (EAV) (107.6TCID50/mL per explant). Impermeability of agarose to virus particles was demonstrated by the absence of labeled microspheres (40 nm) and a lack of EAV-antigens in RK13 cells seeded underneath the agarose layer in which inoculated explants were embedded. At 72 hpi, 27% of the EAV-positive cells were CD172a+ and 19% were CD3+ in nasal explants and 45% of the EAV-positive cells were CD172a+ and 15% were CD3+ in nasopharyngeal explants. Only a small percentage of EAV-positive cells were IgM+. This study validates the usefulness of a polarized mucosal explant system and shows that CD172a+ myeloid cells and CD3+ T lymphocytes represent important EAV-target cells in the respiratory mucosa.
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http://dx.doi.org/10.1186/1297-9716-44-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668984PMC
March 2013

Virulent feline calicivirus disease in a shelter in Italy: a case description.

Res Vet Sci 2013 Aug 21;95(1):283-90. Epub 2013 Feb 21.

Department of Veterinary Medical Sciences, Alma Mater Studiorum, University of Bologna, Italy.

Feline calicivirus (FCV) is a common pathogen of cats that is particularly widespread in multi-cat environments such as shelters and catteries. FCV infections are usually associated with acute, mild and self-limiting upper respiratory tract disease characterized by oral vesicles/ulcers. Recently, virulent systemic disease (VSD) associated with FCV infection has been reported in the USA and Europe. This paper describes a case of VSD affecting one adult, FIV infected cat ("Oscar") living in a shelter located in Northern Italy; the clinical, post-mortem and laboratory findings indicate that this is the first case of suspected FCV-VSD in this country. Similar to a previous report (Meyer et al., 2011), the disease affected only one cat, while others remained asymptomatic, despite their direct contact with "Oscar". Phylogenetic analysis identified unique features in the "Oscar" FCV isolate. The FIV infection of the patient might have favoured the generation of the virulent FCV strains in this cat.
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http://dx.doi.org/10.1016/j.rvsc.2013.01.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7111799PMC
August 2013

Orf in South Africa: endemic but neglected.

Onderstepoort J Vet Res 2012 Dec 7;79(1):E1-8. Epub 2012 Dec 7.

Dipartimento di Scienze Mediche Veterinarie, University of Bologna.

A survey amongst sheep and goat producers and veterinarians was undertaken to collect epidemiological data on orf in South Africa. Previous epidemiological studies on the presence of the disease in the country have not been documented and this report is the first descriptive epidemiological study of orf in South Africa. A seven-month investigation, realised by direct and indirect interviews and field observation, enabled us to outline incidence and risk factors of this disease and to better understand how the local farmers in rural areas relate to it. The results may contribute to better management of the disease in rural areas. By means of molecular analyses the phylogenetic relationships between field isolates from different areas have been identified. The findings gave a first important contribution to the general assessment of the economic impact of orf virus infections and the extent of the risk to human health.
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http://dx.doi.org/10.4102/ojvr.v79i1.499DOI Listing
December 2012
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