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SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients. Author summary SARS-CoV-2 pandemic has resulted in millions of infections and deaths worldwide, yet the role of host innate immune responses in COVID-19 pathogenesis remains only partially characterized. Innate immunity represents the first line of host defense against viruses. Upon viral recognition, the secretion of type I and III interferons (IFN) establishes the cellular state of viral resistance, and contributes to induce the specific adaptive immune responses. Moving from in vitro evidences on the protective role played by plasmacytoid dendritic cells (pDC)-released type I IFN in the early phase of SARS-CoV-2 infection, here we characterized ex vivo the pDC phenotype and the balance between anti-viral and pro-inflammatory cytokines of COVID-19 patients stratified according to disease severity. Our study confirms in COVID-19 the crucial and protective role of pDC/type I IFN axis, whose deeper understanding may contribute to the development of novel pharmacological strategies and/or host-directed therapies aimed at boosting pDC response since the early phases of SARS-CoV-2 infection.
Martina Severa; Roberta A. Diotti; Marilena P. Etna; Fabiana Rizzo; Stefano Fiore; Daniela Ricci; Marco Iannetta; Alessandro Sinigaglia; Alessandra Lodi; Nicasio Mancini; Elena Criscuolo; Massimo Clementi; Massimo Andreoni; Stefano Balducci; Luisa Barzon; Paola Stefanelli; Nicola Clementi; Eliana M. Coccia. Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection. 2021, 1 .
AMA StyleMartina Severa, Roberta A. Diotti, Marilena P. Etna, Fabiana Rizzo, Stefano Fiore, Daniela Ricci, Marco Iannetta, Alessandro Sinigaglia, Alessandra Lodi, Nicasio Mancini, Elena Criscuolo, Massimo Clementi, Massimo Andreoni, Stefano Balducci, Luisa Barzon, Paola Stefanelli, Nicola Clementi, Eliana M. Coccia. Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection. . 2021; ():1.
Chicago/Turabian StyleMartina Severa; Roberta A. Diotti; Marilena P. Etna; Fabiana Rizzo; Stefano Fiore; Daniela Ricci; Marco Iannetta; Alessandro Sinigaglia; Alessandra Lodi; Nicasio Mancini; Elena Criscuolo; Massimo Clementi; Massimo Andreoni; Stefano Balducci; Luisa Barzon; Paola Stefanelli; Nicola Clementi; Eliana M. Coccia. 2021. "Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection." , no. : 1.
Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.
Federico Gobbi; Dora Buonfrate; Lucia Moro; Paola Rodari; Chiara Piubelli; Sara Caldrer; Silvia Riccetti; Alessandro Sinigaglia; Luisa Barzon. Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection. Viruses 2021, 13, 422 .
AMA StyleFederico Gobbi, Dora Buonfrate, Lucia Moro, Paola Rodari, Chiara Piubelli, Sara Caldrer, Silvia Riccetti, Alessandro Sinigaglia, Luisa Barzon. Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection. Viruses. 2021; 13 (3):422.
Chicago/Turabian StyleFederico Gobbi; Dora Buonfrate; Lucia Moro; Paola Rodari; Chiara Piubelli; Sara Caldrer; Silvia Riccetti; Alessandro Sinigaglia; Luisa Barzon. 2021. "Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection." Viruses 13, no. 3: 422.
In this Review, we briefly describe the basic virology and pathogenesis of SARS-CoV-2, highlighting how stem cell technology and organoids can contribute to the understanding of SARS-CoV-2 cell tropisms and the mechanism of disease in the human host, supporting and clarifying findings from clinical studies in infected individuals. We summarize here the results of studies, which used these technologies to investigate SARS-CoV-2 pathogenesis in different organs. Studies with in vitro models of lung epithelia showed that alveolar epithelial type II cells, but not differentiated lung alveolar epithelial type I cells, are key targets of SARS-CoV-2, which triggers cell apoptosis and inflammation, while impairing surfactant production. Experiments with human small intestinal organoids and colonic organoids showed that the gastrointestinal tract is another relevant target for SARS-CoV-2. The virus can infect and replicate in enterocytes and cholangiocytes, inducing cell damage and inflammation. Direct viral damage was also demonstrated in in vitro models of human cardiomyocytes and choroid plexus epithelial cells. At variance, endothelial cells and neurons are poorly susceptible to viral infection, thus supporting the hypothesis that neurological symptoms and vascular damage result from the indirect effects of systemic inflammatory and immunological hyper-responses to SARS-CoV-2 infection.
Marta Trevisan; Silvia Riccetti; Alessandro Sinigaglia; Luisa Barzon. SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids. International Journal of Molecular Sciences 2021, 22, 2356 .
AMA StyleMarta Trevisan, Silvia Riccetti, Alessandro Sinigaglia, Luisa Barzon. SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids. International Journal of Molecular Sciences. 2021; 22 (5):2356.
Chicago/Turabian StyleMarta Trevisan; Silvia Riccetti; Alessandro Sinigaglia; Luisa Barzon. 2021. "SARS-CoV-2 Infection and Disease Modelling Using Stem Cell Technology and Organoids." International Journal of Molecular Sciences 22, no. 5: 2356.
A Correction to this paper has been published: https://doi.org/10.1038/s41586-020-2956-7.
Enrico Lavezzo; Elisa Franchin; Constanze Ciavarella; Gina Cuomo-Dannenburg; Luisa Barzon; Claudia Del Vecchio; Lucia Rossi; Riccardo Manganelli; Arianna Loregian; Nicolò Navarin; Davide Abate; Manuela Sciro; Stefano Merigliano; Ettore De Canale; Maria Cristina Vanuzzo; Valeria Besutti; Francesca Saluzzo; Francesco Onelia; Monia Pacenti; Saverio G. Parisi; Giovanni Carretta; Daniele Donato; Luciano Flor; Silvia Cocchio; Giulia Masi; Alessandro Sperduti; Lorenzo Cattarino; Renato Salvador; Michele Nicoletti; Federico Caldart; Gioele Castelli; Eleonora Nieddu; Beatrice Labella; Ludovico Fava; Matteo Drigo; Katy A. M. Gaythorpe; Alessandra R. Brazzale; Stefano Toppo; Marta Trevisan; Vincenzo Baldo; Christl A. Donnelly; Neil M. Ferguson; Ilaria Dorigatti; Andrea Crisanti. Author Correction: Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 2021, 590, E11 -E11.
AMA StyleEnrico Lavezzo, Elisa Franchin, Constanze Ciavarella, Gina Cuomo-Dannenburg, Luisa Barzon, Claudia Del Vecchio, Lucia Rossi, Riccardo Manganelli, Arianna Loregian, Nicolò Navarin, Davide Abate, Manuela Sciro, Stefano Merigliano, Ettore De Canale, Maria Cristina Vanuzzo, Valeria Besutti, Francesca Saluzzo, Francesco Onelia, Monia Pacenti, Saverio G. Parisi, Giovanni Carretta, Daniele Donato, Luciano Flor, Silvia Cocchio, Giulia Masi, Alessandro Sperduti, Lorenzo Cattarino, Renato Salvador, Michele Nicoletti, Federico Caldart, Gioele Castelli, Eleonora Nieddu, Beatrice Labella, Ludovico Fava, Matteo Drigo, Katy A. M. Gaythorpe, Alessandra R. Brazzale, Stefano Toppo, Marta Trevisan, Vincenzo Baldo, Christl A. Donnelly, Neil M. Ferguson, Ilaria Dorigatti, Andrea Crisanti. Author Correction: Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature. 2021; 590 (7844):E11-E11.
Chicago/Turabian StyleEnrico Lavezzo; Elisa Franchin; Constanze Ciavarella; Gina Cuomo-Dannenburg; Luisa Barzon; Claudia Del Vecchio; Lucia Rossi; Riccardo Manganelli; Arianna Loregian; Nicolò Navarin; Davide Abate; Manuela Sciro; Stefano Merigliano; Ettore De Canale; Maria Cristina Vanuzzo; Valeria Besutti; Francesca Saluzzo; Francesco Onelia; Monia Pacenti; Saverio G. Parisi; Giovanni Carretta; Daniele Donato; Luciano Flor; Silvia Cocchio; Giulia Masi; Alessandro Sperduti; Lorenzo Cattarino; Renato Salvador; Michele Nicoletti; Federico Caldart; Gioele Castelli; Eleonora Nieddu; Beatrice Labella; Ludovico Fava; Matteo Drigo; Katy A. M. Gaythorpe; Alessandra R. Brazzale; Stefano Toppo; Marta Trevisan; Vincenzo Baldo; Christl A. Donnelly; Neil M. Ferguson; Ilaria Dorigatti; Andrea Crisanti. 2021. "Author Correction: Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’." Nature 590, no. 7844: E11-E11.
A workflow for rapid SARS-CoV-2 epitope discovery on peptide microarrays is herein reported. The process started with a proteome-wide screening of immunoreactivity based on the use of a high-density microarray followed by a refinement and validation phase on a restricted panel of probes using microarrays with tailored peptide immobilization through a click-based strategy. Progressively larger, independent cohorts of Covid-19 positive sera were tested in the refinement processes, leading to the identification of immunodominant regions on SARS-CoV-2 spike (S), nucleocapsid (N) protein and Orf1ab polyprotein. A summary study testing 50 serum samples highlighted an epitope of the N protein (region 155–71) providing good diagnostic performance in discriminating Covid-19 positive vs. healthy individuals. Using this epitope, 92% sensitivity and 100% specificity were reached for IgG detection in Covid-19 samples, and no cross-reactivity with common cold coronaviruses was detected. Likewise, IgM immunoreactivity in samples collected within the first month after symptoms onset showed discrimination ability. Overall, epitope 155–171 from N protein represents a promising candidate for further development and rapid implementation in serological tests.
Angelo Musicò; Roberto Frigerio; Alessandro Mussida; Luisa Barzon; Alessandro Sinigaglia; Silvia Riccetti; Federico Gobbi; Chiara Piubelli; Greta Bergamaschi; Marcella Chiari; Alessandro Gori; Marina Cretich. SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region. Vaccines 2021, 9, 35 .
AMA StyleAngelo Musicò, Roberto Frigerio, Alessandro Mussida, Luisa Barzon, Alessandro Sinigaglia, Silvia Riccetti, Federico Gobbi, Chiara Piubelli, Greta Bergamaschi, Marcella Chiari, Alessandro Gori, Marina Cretich. SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region. Vaccines. 2021; 9 (1):35.
Chicago/Turabian StyleAngelo Musicò; Roberto Frigerio; Alessandro Mussida; Luisa Barzon; Alessandro Sinigaglia; Silvia Riccetti; Federico Gobbi; Chiara Piubelli; Greta Bergamaschi; Marcella Chiari; Alessandro Gori; Marina Cretich. 2021. "SARS-CoV-2 Epitope Mapping on Microarrays Highlights Strong Immune-Response to N Protein Region." Vaccines 9, no. 1: 35.
Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the most lethal infectious diseases with estimates of approximately 1.4 million human deaths in 2018. M. tuberculosis has a well-established ability to circumvent the host immune system to ensure its intracellular survival and persistence in the host. Mechanisms include subversion of expression of key microRNAs (miRNAs) involved in the regulation of host innate and adaptive immune response against M. tuberculosis. Several studies have reported differential expression of miRNAs during active TB and latent tuberculosis infection (LTBI), suggesting their potential use as biomarkers of disease progression and response to anti-TB therapy. This review focused on the miRNAs involved in TB pathogenesis and on the mechanism through which miRNAs induced during TB modulate cell antimicrobial responses. An attentive study of the recent literature identifies a group of miRNAs, which are differentially expressed in active TB vs. LTBI or vs. treated TB and can be proposed as candidate biomarkers.
Alessandro Sinigaglia; Elektra Peta; Silvia Riccetti; Seshasailam Venkateswaran; Riccardo Manganelli; Luisa Barzon. Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers. Cells 2020, 9, 2160 .
AMA StyleAlessandro Sinigaglia, Elektra Peta, Silvia Riccetti, Seshasailam Venkateswaran, Riccardo Manganelli, Luisa Barzon. Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers. Cells. 2020; 9 (10):2160.
Chicago/Turabian StyleAlessandro Sinigaglia; Elektra Peta; Silvia Riccetti; Seshasailam Venkateswaran; Riccardo Manganelli; Luisa Barzon. 2020. "Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers." Cells 9, no. 10: 2160.
West Nile virus (WNV) and Usutu virus (USUV) are genetically related neurotropic mosquito-borne flaviviruses, which frequently co-circulate in nature. Despite USUV seeming to be less pathogenic for humans than WNV, the clinical manifestations induced by these two viruses often overlap and may evolve to produce severe neurological complications. The aim of this study was to investigate the effects of WNV and USUV infection on human induced pluripotent stem cell-derived neural stem cells (hNSCs), as a model of the neural progenitor cells in the developing fetal brain and in adult brain. Zika virus (ZIKV), a flavivirus with known tropism for NSCs, was used as the positive control. Infection of hNSCs and viral production, effects on cell viability, apoptosis, and innate antiviral responses were compared among viruses. WNV displayed the highest replication efficiency and cytopathic effects in hNSCs, followed by USUV and then ZIKV. In these cells, both WNV and USUV induced the overexpression of innate antiviral response genes at significantly higher levels than ZIKV. Expression of interferon type I, interleukin-1β and caspase-3 was significantly more elevated in WNV- than USUV-infected hNSCs, in agreement with the higher neuropathogenicity of WNV and the ability to inhibit the interferon response pathway.
Silvia Riccetti; Alessandro Sinigaglia; Giovanna Desole; Norbert Nowotny; Marta Trevisan; Luisa Barzon. Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells. Viruses 2020, 12, 882 .
AMA StyleSilvia Riccetti, Alessandro Sinigaglia, Giovanna Desole, Norbert Nowotny, Marta Trevisan, Luisa Barzon. Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells. Viruses. 2020; 12 (8):882.
Chicago/Turabian StyleSilvia Riccetti; Alessandro Sinigaglia; Giovanna Desole; Norbert Nowotny; Marta Trevisan; Luisa Barzon. 2020. "Modelling West Nile Virus and Usutu Virus Pathogenicity in Human Neural Stem Cells." Viruses 12, no. 8: 882.
On the 21st of February 2020 a resident of the municipality of Vo’, a small town near Padua, died of pneumonia due to SARS-CoV-2 infection1. This was the first COVID-19 death detected in Italy since the emergence of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. We collected information on the demography, clinical presentation, hospitalization, contact network and presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo’ at two consecutive time points. On the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI) 2.1-3.3%). On the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% Confidence Interval (CI) 0.8-1.8%). Notably, 42.5% (95% CI 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (i.e. did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (p-values 0.62 and 0.74 for E and RdRp genes, respectively, Exact Wilcoxon-Mann-Whitney test). This study sheds new light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides new insights into its transmission dynamics and the efficacy of the implemented control measures.
Enrico Lavezzo; Elisa Franchin; Constanze Ciavarella; Gina Cuomo-Dannenburg; Luisa Barzon; Claudia Del Vecchio; Lucia Rossi; Riccardo Manganelli; Arianna Loregian; Nicolò Navarin; Davide Abate; Manuela Sciro; Stefano Merigliano; Ettore De Canale; Maria Cristina Vanuzzo; Valeria Besutti; Francesca Saluzzo; Francesco Onelia; Monia Pacenti; Saverio G. Parisi; Giovanni Carretta; Daniele Donato; Luciano Flor; Silvia Cocchio; Giulia Masi; Alessandro Sperduti; Lorenzo Cattarino; Renato Salvador; Michele Nicoletti; Federico Caldart; Gioele Castelli; Eleonora Nieddu; Beatrice Labella; Ludovico Fava; Matteo Drigo; Katy A. M. Gaythorpe; Alessandra R. Brazzale; Stefano Toppo; Marta Trevisan; Vincenzo Baldo; Christl A. Donnelly; Neil M. Ferguson; Ilaria Dorigatti; Andrea Crisanti; Kylie E. C. Ainslie; Marc Baguelin; Samir Bhatt; Adhiratha Boonyasiri; Olivia Boyd; Helen L. Coupland; Zulma Cucunubá; Bimandra A. Djafaara; Sabine L. van Elsland; Rich FitzJohn; Seth Flaxman; Will D. Green; Timothy Hallett; Arran Hamlet; David Haw; Natsuko Imai; Benjamin Jeffrey; Edward Knock; Daniel J. Laydon; Thomas Mellan; Swapnil Mishra; Gemma Nedjati-Gilani; Pierre Nouvellet; Lucy C. Okell; Kris V. Parag; Steven Riley; Hayley A. Thompson; H. Juliette T. Unwin; Robert Verity; Michaela A. C. Vollmer; Patrick G. T. Walker; Caroline E. Walters; Haowei Wang; Yuanrong Wang; Oliver J. Watson; Charles Whittaker; Lilith K. Whittles; Xiaoyue Xi; Imperial College COVID-19 Response Team. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 2020, 584, 425 -429.
AMA StyleEnrico Lavezzo, Elisa Franchin, Constanze Ciavarella, Gina Cuomo-Dannenburg, Luisa Barzon, Claudia Del Vecchio, Lucia Rossi, Riccardo Manganelli, Arianna Loregian, Nicolò Navarin, Davide Abate, Manuela Sciro, Stefano Merigliano, Ettore De Canale, Maria Cristina Vanuzzo, Valeria Besutti, Francesca Saluzzo, Francesco Onelia, Monia Pacenti, Saverio G. Parisi, Giovanni Carretta, Daniele Donato, Luciano Flor, Silvia Cocchio, Giulia Masi, Alessandro Sperduti, Lorenzo Cattarino, Renato Salvador, Michele Nicoletti, Federico Caldart, Gioele Castelli, Eleonora Nieddu, Beatrice Labella, Ludovico Fava, Matteo Drigo, Katy A. M. Gaythorpe, Alessandra R. Brazzale, Stefano Toppo, Marta Trevisan, Vincenzo Baldo, Christl A. Donnelly, Neil M. Ferguson, Ilaria Dorigatti, Andrea Crisanti, Kylie E. C. Ainslie, Marc Baguelin, Samir Bhatt, Adhiratha Boonyasiri, Olivia Boyd, Helen L. Coupland, Zulma Cucunubá, Bimandra A. Djafaara, Sabine L. van Elsland, Rich FitzJohn, Seth Flaxman, Will D. Green, Timothy Hallett, Arran Hamlet, David Haw, Natsuko Imai, Benjamin Jeffrey, Edward Knock, Daniel J. Laydon, Thomas Mellan, Swapnil Mishra, Gemma Nedjati-Gilani, Pierre Nouvellet, Lucy C. Okell, Kris V. Parag, Steven Riley, Hayley A. Thompson, H. Juliette T. Unwin, Robert Verity, Michaela A. C. Vollmer, Patrick G. T. Walker, Caroline E. Walters, Haowei Wang, Yuanrong Wang, Oliver J. Watson, Charles Whittaker, Lilith K. Whittles, Xiaoyue Xi, Imperial College COVID-19 Response Team. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature. 2020; 584 (7821):425-429.
Chicago/Turabian StyleEnrico Lavezzo; Elisa Franchin; Constanze Ciavarella; Gina Cuomo-Dannenburg; Luisa Barzon; Claudia Del Vecchio; Lucia Rossi; Riccardo Manganelli; Arianna Loregian; Nicolò Navarin; Davide Abate; Manuela Sciro; Stefano Merigliano; Ettore De Canale; Maria Cristina Vanuzzo; Valeria Besutti; Francesca Saluzzo; Francesco Onelia; Monia Pacenti; Saverio G. Parisi; Giovanni Carretta; Daniele Donato; Luciano Flor; Silvia Cocchio; Giulia Masi; Alessandro Sperduti; Lorenzo Cattarino; Renato Salvador; Michele Nicoletti; Federico Caldart; Gioele Castelli; Eleonora Nieddu; Beatrice Labella; Ludovico Fava; Matteo Drigo; Katy A. M. Gaythorpe; Alessandra R. Brazzale; Stefano Toppo; Marta Trevisan; Vincenzo Baldo; Christl A. Donnelly; Neil M. Ferguson; Ilaria Dorigatti; Andrea Crisanti; Kylie E. C. Ainslie; Marc Baguelin; Samir Bhatt; Adhiratha Boonyasiri; Olivia Boyd; Helen L. Coupland; Zulma Cucunubá; Bimandra A. Djafaara; Sabine L. van Elsland; Rich FitzJohn; Seth Flaxman; Will D. Green; Timothy Hallett; Arran Hamlet; David Haw; Natsuko Imai; Benjamin Jeffrey; Edward Knock; Daniel J. Laydon; Thomas Mellan; Swapnil Mishra; Gemma Nedjati-Gilani; Pierre Nouvellet; Lucy C. Okell; Kris V. Parag; Steven Riley; Hayley A. Thompson; H. Juliette T. Unwin; Robert Verity; Michaela A. C. Vollmer; Patrick G. T. Walker; Caroline E. Walters; Haowei Wang; Yuanrong Wang; Oliver J. Watson; Charles Whittaker; Lilith K. Whittles; Xiaoyue Xi; Imperial College COVID-19 Response Team. 2020. "Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’." Nature 584, no. 7821: 425-429.
West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients’ samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity.
Monia Pacenti; Alessandro Sinigaglia; Elisa Franchin; Silvana Pagni; Enrico Lavezzo; Fabrizio Montarsi; Gioia Capelli; Luisa Barzon. Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings. Viruses 2020, 12, 458 .
AMA StyleMonia Pacenti, Alessandro Sinigaglia, Elisa Franchin, Silvana Pagni, Enrico Lavezzo, Fabrizio Montarsi, Gioia Capelli, Luisa Barzon. Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings. Viruses. 2020; 12 (4):458.
Chicago/Turabian StyleMonia Pacenti; Alessandro Sinigaglia; Elisa Franchin; Silvana Pagni; Enrico Lavezzo; Fabrizio Montarsi; Gioia Capelli; Luisa Barzon. 2020. "Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings." Viruses 12, no. 4: 458.
Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor. Cytotoxicity was subsequently evaluated in the same cells after the uptake of the nanoparticles. Internalization of nanocarriers loaded with the anticancer drug 3N-cyclopropylmethyl-7-phenyl-pyrrolo- quinolinone (MG2477) into cells resulted in a substantial increase of the cytotoxicity with respect to the free formulation. Targeting with anti-CD44v6 antibodies or HA yielded nanoparticles with similar effectiveness, in their optimized formulation.
Lucía Morillas Becerril; Elektra Peta; Luca Gabrielli; Venera Russo; Elisa Lubian; Luca Nodari; Maria Grazia Ferlin; Paolo Scrimin; Giorgio Palù; Luisa Barzon; Ignazio Castagliuolo; Fabrizio Mancin; Marta Trevisan. Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells. Nanomaterials 2020, 10, 298 .
AMA StyleLucía Morillas Becerril, Elektra Peta, Luca Gabrielli, Venera Russo, Elisa Lubian, Luca Nodari, Maria Grazia Ferlin, Paolo Scrimin, Giorgio Palù, Luisa Barzon, Ignazio Castagliuolo, Fabrizio Mancin, Marta Trevisan. Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells. Nanomaterials. 2020; 10 (2):298.
Chicago/Turabian StyleLucía Morillas Becerril; Elektra Peta; Luca Gabrielli; Venera Russo; Elisa Lubian; Luca Nodari; Maria Grazia Ferlin; Paolo Scrimin; Giorgio Palù; Luisa Barzon; Ignazio Castagliuolo; Fabrizio Mancin; Marta Trevisan. 2020. "Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells." Nanomaterials 10, no. 2: 298.
Introduction: West Nile virus (WNV) is a neurotropic mosquito-borne flavivirus, which is endemic in many countries, especially in Europe and in North America, where the virus has increased its activity in the recent years. No vaccines nor antiviral drugs are available for the prevention and treatment of WNV infection in humans.Areas covered: This review article describes viral and host targets that have been addressed by anti-WNV drug discovery studies and summarizes the most relevant anti-WNV candidate compounds identified so far, focusing on those showing antiviral efficacy in in vivo models and broad-spectrum anti-flavivirus activity.Expert opinion: The most promising anti-WNV drug candidates target conserved enzymatic motifs in viral NS3 protease and NS5 polymerase and are effective against different flaviviruses. Targeting host factors required for viral infection and replication and modulation of host innate antiviral response are also promising approaches, which may lead to the development of compounds with broad-spectrum antiviral activity, a desirable feature for an antiviral drug.
Alessandro Sinigaglia; Elektra Peta; Silvia Riccetti; Luisa Barzon. New avenues for therapeutic discovery against West Nile virus. Expert Opinion on Drug Discovery 2020, 15, 333 -348.
AMA StyleAlessandro Sinigaglia, Elektra Peta, Silvia Riccetti, Luisa Barzon. New avenues for therapeutic discovery against West Nile virus. Expert Opinion on Drug Discovery. 2020; 15 (3):333-348.
Chicago/Turabian StyleAlessandro Sinigaglia; Elektra Peta; Silvia Riccetti; Luisa Barzon. 2020. "New avenues for therapeutic discovery against West Nile virus." Expert Opinion on Drug Discovery 15, no. 3: 333-348.
Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view.
Francesco Nicoli; Barbara Mantelli; Eleonora Gallerani; Valentina Telatin; Irene Bonazzi; Peggy Marconi; Riccardo Gavioli; Liliana Gabrielli; Tiziana Lazzarotto; Luisa Barzon; Giorgio Palù; And Antonella Caputo. HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy. Vaccines 2020, 8, 26 .
AMA StyleFrancesco Nicoli, Barbara Mantelli, Eleonora Gallerani, Valentina Telatin, Irene Bonazzi, Peggy Marconi, Riccardo Gavioli, Liliana Gabrielli, Tiziana Lazzarotto, Luisa Barzon, Giorgio Palù, And Antonella Caputo. HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy. Vaccines. 2020; 8 (1):26.
Chicago/Turabian StyleFrancesco Nicoli; Barbara Mantelli; Eleonora Gallerani; Valentina Telatin; Irene Bonazzi; Peggy Marconi; Riccardo Gavioli; Liliana Gabrielli; Tiziana Lazzarotto; Luisa Barzon; Giorgio Palù; And Antonella Caputo. 2020. "HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy." Vaccines 8, no. 1: 26.
Despite efforts to improve surveillance and vaccination coverage, measles virus (MeV) continues to cause outbreaks also in high-income countries. As the reference laboratory of the Veneto Region, Italy, we analyzed changes in population immunity, described measles outbreaks, investigated MeV genetic diversity, and evaluated cross-protection of measles vaccination against MeV epidemic strains. Like most European areas, the Veneto Region has suboptimal measles vaccination coverage and is facing a growing public mistrust of vaccination. A progressive decline of measles vaccine uptake was observed during the last decade in the Veneto Region, leading to immunity gaps in children and young adults. Measles outbreaks were caused by the same MeV genotype B3, D4, and D8 strains that were circulating in other European countries. Eleven cases of measles were observed in immunized subjects. These cases were not associated with particular MeV genotypes nor with mutations in epitopes recognized by neutralizing antibodies. Accordingly, sera from fully vaccinated subjects cross-neutralized epidemic MeV strains, including the genotypes B3, D4, and D8, with the same high efficiency demonstrated against the vaccine strain. In fully vaccinated subjects, high MeV IgG antibody titers persisted up to 30 years following vaccination. These results support the use of the current measles-containing vaccines and strategies to strengthen vaccination.
Monia Pacenti; Nataskya Maione; Enrico Lavezzo; Elisa Franchin; Federico Dal Bello; Lorena Gottardello; Luisa Barzon. Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting. Vaccines 2019, 7, 199 .
AMA StyleMonia Pacenti, Nataskya Maione, Enrico Lavezzo, Elisa Franchin, Federico Dal Bello, Lorena Gottardello, Luisa Barzon. Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting. Vaccines. 2019; 7 (4):199.
Chicago/Turabian StyleMonia Pacenti; Nataskya Maione; Enrico Lavezzo; Elisa Franchin; Federico Dal Bello; Lorena Gottardello; Luisa Barzon. 2019. "Measles Virus Infection and Immunity in a Suboptimal Vaccination Coverage Setting." Vaccines 7, no. 4: 199.
Background Usutu virus (USUV) is a mosquito-borne flavivirus, which shares its transmission cycle with the phylogenetically related West Nile virus (WNV). USUV circulates in several European countries and its activity has increased over the last 5 years. Aim To describe human cases of USUV infection identified by surveillance for WNV and USUV infection in the Veneto Region of northern Italy in 2018. Methods From 1 June to 30 November 2018, all cases of suspected autochthonous arbovirus infection and blood donors who had a reactive WNV nucleic acid test were investigated for both WNV and USUV infection by in-house molecular methods. Anti-WNV and anti-USUV IgM and IgG antibodies were detected by ELISA and in-house immunofluorescence assay, respectively; positive serum samples were further tested by WNV and USUV neutralisation assays run in parallel. Results Eight cases of USUV infection (one with neuroinvasive disease, six with fever and one viraemic blood donor who developed arthralgia and myalgia) and 427 cases of WNV infection were identified. A remarkable finding of this study was the persistence of USUV RNA in the blood and urine of three patients during follow-up. USUV genome sequences from two patients shared over 99% nt identity with USUV sequences detected in mosquito pools from the same area and clustered within lineage Europe 2. Conclusions Clinical presentation and laboratory findings in patients with USUV infection were similar to those found in patients with WNV infection. Cross-reactivity of serology and molecular tests challenged the differential diagnosis.
Monia Pacenti; Alessandro Sinigaglia; Thomas Martello; Maria Elena De Rui; Elisa Franchin; Silvana Pagni; Elektra Peta; Silvia Riccetti; Adelaide Milani; Fabrizio Montarsi; Gioia Capelli; Carlo Giovanni Doroldi; Francesco Bigolin; Luca Santelli; Lucia Nardetto; Marco Zoccarato; Luisa Barzon. Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018. Eurosurveillance 2019, 24, 1900180 .
AMA StyleMonia Pacenti, Alessandro Sinigaglia, Thomas Martello, Maria Elena De Rui, Elisa Franchin, Silvana Pagni, Elektra Peta, Silvia Riccetti, Adelaide Milani, Fabrizio Montarsi, Gioia Capelli, Carlo Giovanni Doroldi, Francesco Bigolin, Luca Santelli, Lucia Nardetto, Marco Zoccarato, Luisa Barzon. Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018. Eurosurveillance. 2019; 24 (47):1900180.
Chicago/Turabian StyleMonia Pacenti; Alessandro Sinigaglia; Thomas Martello; Maria Elena De Rui; Elisa Franchin; Silvana Pagni; Elektra Peta; Silvia Riccetti; Adelaide Milani; Fabrizio Montarsi; Gioia Capelli; Carlo Giovanni Doroldi; Francesco Bigolin; Luca Santelli; Lucia Nardetto; Marco Zoccarato; Luisa Barzon. 2019. "Clinical and virological findings in patients with Usutu virus infection, northern Italy, 2018." Eurosurveillance 24, no. 47: 1900180.
Generation of human induced pluripotent stem cells (hiPSCs) and their differentiation into a variety of cells and organoids have allowed setting up versatile, non-invasive, ethically sustainable, and patient-specific models for the investigation of the mechanisms of human diseases, including viral infections and host–pathogen interactions. In this study, we investigated and compared the infectivity and replication kinetics in hiPSCs, hiPSC-derived neural stem cells (NSCs) and undifferentiated neurons, and the effect of viral infection on host innate antiviral responses of representative flaviviruses associated with diverse neurological diseases, i.e., Zika virus (ZIKV), West Nile virus (WNV), and dengue virus (DENV). In addition, we exploited hiPSCs to model ZIKV infection in the embryo and during neurogenesis. The results of this study confirmed the tropism of ZIKV for NSCs, but showed that WNV replicated in these cells with much higher efficiency than ZIKV and DENV, inducing massive cell death. Although with lower efficiency, all flaviviruses could also infect pluripotent stem cells and neurons, inducing similar patterns of antiviral innate immune response gene expression. While showing the usefulness of hiPSC-based infection models, these findings suggest that additional virus-specific mechanisms, beyond neural tropism, are responsible for the peculiarities of disease phenotype in humans.
Giovanna Desole; Alessandro Sinigaglia; Silvia Riccetti; Giulia Masi; Monia Pacenti; Marta Trevisan; Luisa Barzon. Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems. International Journal of Molecular Sciences 2019, 20, 5404 .
AMA StyleGiovanna Desole, Alessandro Sinigaglia, Silvia Riccetti, Giulia Masi, Monia Pacenti, Marta Trevisan, Luisa Barzon. Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems. International Journal of Molecular Sciences. 2019; 20 (21):5404.
Chicago/Turabian StyleGiovanna Desole; Alessandro Sinigaglia; Silvia Riccetti; Giulia Masi; Monia Pacenti; Marta Trevisan; Luisa Barzon. 2019. "Modelling Neurotropic Flavivirus Infection in Human Induced Pluripotent Stem Cell-Derived Systems." International Journal of Molecular Sciences 20, no. 21: 5404.
West Nile Virus (WNV) is a mosquito-transmitted flavivirus which causes encephalitis especially in elderly and immunocompromised individuals. Previous studies have suggested the protective role of the Toll-like receptor 3 (TLR3) pathway against WNV entry into the brain, while the WNV non-structural protein 1 (NS1) interferes with the TLR3 signaling pathway, besides being a component of viral genome replication machinery. In this study, we investigated whether immunization with NS1 could protect against WNV neuroinvasion in the context of TLR3 deficiency. We immunized mice with either an intact or deleted TLR3 system (TLR3KO) with WNV envelope glycoprotein (gE) protein, NS1, or a combination of gE and NS1. Immunization with gE or gE/NS1, but not with NS1 alone, induced WNV neutralizing antibodies and protected against WNV brain invasion and inflammation. The presence of intact TLR3 signaling had no apparent effect on WNV brain invasion. However, mock-immunized TLR3KO mice had higher inflammatory cell invasion upon WNV brain infection than NS1-immunized TLR3KO mice and wild type mice. Thus, immunization against NS1 may reduce brain inflammation in a context of TLR3 signaling deficiency.
Sameera Patel; Alessandro Sinigaglia; Luisa Barzon; Matteo Fassan; Florian Sparber; Salome LeibundGut-Landmann; Mathias Ackermann. Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV. Viruses 2019, 11, 603 .
AMA StyleSameera Patel, Alessandro Sinigaglia, Luisa Barzon, Matteo Fassan, Florian Sparber, Salome LeibundGut-Landmann, Mathias Ackermann. Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV. Viruses. 2019; 11 (7):603.
Chicago/Turabian StyleSameera Patel; Alessandro Sinigaglia; Luisa Barzon; Matteo Fassan; Florian Sparber; Salome LeibundGut-Landmann; Mathias Ackermann. 2019. "Role of NS1 and TLR3 in Pathogenesis and Immunity of WNV." Viruses 11, no. 7: 603.
The present multicentric (n = 11 laboratories) study aimed to identify conversion factors from copies/mL to international units (IU)/mL for the normalization of HCMV DNA load using the first WHO International Standard for HCMV nucleic acid amplification techniques and to enhance interlaboratory agreement of HCMV DNA quantification methods. Study protocols for whole blood and plasma (extraction and amplification) were performed to calculate conversion factors from HCMV DNA copy number to IU. The greatest variability was observed in samples with lower HCMV concentrations (3.0 Log10) in both biological matrices. Overall, 73.1% (206/282) of whole blood and 82.2% (324/394) of plasma samples analyzed fell within an acceptable variation range (±0.5 Log10 difference). An average of 0.64 (range 0.21–1.17) was the conversion factor calculated for the HCMV whole blood panel and 0.82 (range 0.39–2.2) for the HCMV plasma panel.
Francesca Sidoti; Antonio Piralla; Cristina Costa; Maria Luisa Scarasciulli; Agata Calvario; Pier Giulio Conaldi; Pierpaolo Paba; Carlo Federico Perno; Aurelia Gaeta; Guido Antonelli; Giuseppe Sodano; Rosaria Santangelo; Maurizio Sanguinetti; Maria Linda Vatteroni; Luisa Barzon; Giorgio Palù; Isabella Abbate; Maria Rosaria Capobianchi; Giulia Piccirilli; Tiziana Lazzarotto; Fausto Baldanti; Rossana Cavallo. Collaborative national multicenter for the identification of conversion factors from copies/mL to international units/mL for the normalization of HCMV DNA load. Diagnostic Microbiology and Infectious Disease 2019, 95, 152 -158.
AMA StyleFrancesca Sidoti, Antonio Piralla, Cristina Costa, Maria Luisa Scarasciulli, Agata Calvario, Pier Giulio Conaldi, Pierpaolo Paba, Carlo Federico Perno, Aurelia Gaeta, Guido Antonelli, Giuseppe Sodano, Rosaria Santangelo, Maurizio Sanguinetti, Maria Linda Vatteroni, Luisa Barzon, Giorgio Palù, Isabella Abbate, Maria Rosaria Capobianchi, Giulia Piccirilli, Tiziana Lazzarotto, Fausto Baldanti, Rossana Cavallo. Collaborative national multicenter for the identification of conversion factors from copies/mL to international units/mL for the normalization of HCMV DNA load. Diagnostic Microbiology and Infectious Disease. 2019; 95 (2):152-158.
Chicago/Turabian StyleFrancesca Sidoti; Antonio Piralla; Cristina Costa; Maria Luisa Scarasciulli; Agata Calvario; Pier Giulio Conaldi; Pierpaolo Paba; Carlo Federico Perno; Aurelia Gaeta; Guido Antonelli; Giuseppe Sodano; Rosaria Santangelo; Maurizio Sanguinetti; Maria Linda Vatteroni; Luisa Barzon; Giorgio Palù; Isabella Abbate; Maria Rosaria Capobianchi; Giulia Piccirilli; Tiziana Lazzarotto; Fausto Baldanti; Rossana Cavallo. 2019. "Collaborative national multicenter for the identification of conversion factors from copies/mL to international units/mL for the normalization of HCMV DNA load." Diagnostic Microbiology and Infectious Disease 95, no. 2: 152-158.
In 2018, there was a large West Nile virus (WNV) outbreak in northern Italy. We observed five atypical cases of WNV infection that were characterised by the presence of WNV RNA and WNV IgG at the time of diagnosis, but no IgM response during follow-up. Neutralisation assays demonstrated pre-existing Usutu virus immunity in all patients. Besides challenging diagnosis, the immunological crosstalk between the two viruses warrants further investigation on possible cross-protection or infection enhancement effects.
Alessandro Sinigaglia; Monia Pacenti; Thomas Martello; Silvana Pagni; Elisa Franchin; Luisa Barzon. West Nile virus infection in individuals with pre-existing Usutu virus immunity, northern Italy, 2018. Eurosurveillance 2019, 24, 1900261 .
AMA StyleAlessandro Sinigaglia, Monia Pacenti, Thomas Martello, Silvana Pagni, Elisa Franchin, Luisa Barzon. West Nile virus infection in individuals with pre-existing Usutu virus immunity, northern Italy, 2018. Eurosurveillance. 2019; 24 (21):1900261.
Chicago/Turabian StyleAlessandro Sinigaglia; Monia Pacenti; Thomas Martello; Silvana Pagni; Elisa Franchin; Luisa Barzon. 2019. "West Nile virus infection in individuals with pre-existing Usutu virus immunity, northern Italy, 2018." Eurosurveillance 24, no. 21: 1900261.
Targeted amplicon sequencing of the 16S ribosomal RNA gene is one of the key tools for studying microbial diversity. The accuracy of this approach strongly depends on the choice of primer pairs and, in particular, on the balance between efficiency, specificity and sensitivity in the amplification of the different bacterial 16S sequences contained in a sample. There is thus the need for computational methods to design optimal bacterial 16S primers able to take into account the knowledge provided by the new sequencing technologies. We propose here a computational method for optimizing the choice of primer sets, based on multi-objective optimization, which simultaneously: 1) maximizes efficiency and specificity of target amplification; 2) maximizes the number of different bacterial 16S sequences matched by at least one primer; 3) minimizes the differences in the number of primers matching each bacterial 16S sequence. Our algorithm can be applied to any desired amplicon length without affecting computational performance. The source code of the developed algorithm is released as the mopo16S software tool (Multi-Objective Primer Optimization for 16S experiments) under the GNU General Public License and is available at http://sysbiobig.dei.unipd.it/?q=Software#mopo16S . Results show that our strategy is able to find better primer pairs than the ones available in the literature according to all three optimization criteria. We also experimentally validated three of the primer pairs identified by our method on multiple bacterial species, belonging to different genera and phyla. Results confirm the predicted efficiency and the ability to maximize the number of different bacterial 16S sequences matched by primers.
Francesco Sambo; Francesca Finotello; Enrico Lavezzo; Giacomo Baruzzo; Giulia Masi; Elektra Peta; Marco Falda; Stefano Toppo; Luisa Barzon; Barbara Di Camillo. Optimizing PCR primers targeting the bacterial 16S ribosomal RNA gene. BMC Bioinformatics 2018, 19, 343 .
AMA StyleFrancesco Sambo, Francesca Finotello, Enrico Lavezzo, Giacomo Baruzzo, Giulia Masi, Elektra Peta, Marco Falda, Stefano Toppo, Luisa Barzon, Barbara Di Camillo. Optimizing PCR primers targeting the bacterial 16S ribosomal RNA gene. BMC Bioinformatics. 2018; 19 (1):343.
Chicago/Turabian StyleFrancesco Sambo; Francesca Finotello; Enrico Lavezzo; Giacomo Baruzzo; Giulia Masi; Elektra Peta; Marco Falda; Stefano Toppo; Luisa Barzon; Barbara Di Camillo. 2018. "Optimizing PCR primers targeting the bacterial 16S ribosomal RNA gene." BMC Bioinformatics 19, no. 1: 343.
During the last decades, arboviruses that are endemic in Europe have expanded their geographic range and caused an increasing number of human outbreaks. These viruses include West Nile virus, which is expanding its area of circulation in central and southern Europe; Usutu virus, with increasing evidence of a role in human disease; tick-borne encephalitis virus, which is being detected in northern areas and at higher altitudes as a consequence of climate warming; Crimean-Congo hemorrhagic fever virus, which is endemic in Eastern Europe and the Middle East, but has been recently detected in Spain; other viruses, such as California encephalitis virus antigenic group, which circulate in northern and central Europe but whose relevance for human disease in largely unknown. In addition, the rise in global travel and trade has posed Europe to an increased risk of introduction and expansion of exotic arthropod vectors and autochthonous transmission of arboviruses, like dengue and chikungunya viruses, following new introductions from endemic areas. Implementation of integrated arbovirus surveillance programs has been crucial to adopt proper control measures. The identification of emerging outbreaks is however challenging are requires a high degree of awareness and laboratory capacity, especially for the most neglected but potentially threatening pathogens.
Luisa Barzon. Ongoing and emerging arbovirus threats in Europe. Journal of Clinical Virology 2018, 107, 38 -47.
AMA StyleLuisa Barzon. Ongoing and emerging arbovirus threats in Europe. Journal of Clinical Virology. 2018; 107 ():38-47.
Chicago/Turabian StyleLuisa Barzon. 2018. "Ongoing and emerging arbovirus threats in Europe." Journal of Clinical Virology 107, no. : 38-47.