This page has only limited features, please log in for full access.
Gianni Gori Savellini has experience in basic virology acquired during his PhD studies. He focuses on the study of innate immunity in phlebovirus infection, in particular due to Toscana virus. Following a mature wealth of experience in this field, he has transferred his knowledge to the study of SARS-CoV-2.
Emerging and re-emerging viral infections have been an important public health problem in recent years. We focused our attention on Toscana virus (TOSV), an emergent neurotropic negative-strand RNA virus of the Phenuiviridae family. The mechanisms of protection against phlebovirus natural infection are not known; however, it is supposed that a virus-neutralizing antibody response against viral glycoproteins would be useful to block the first stages of infection. By using an improved memory B cell immortalization method, we obtained a panel of human mAbs which reacted with TOSV antigens. We identified three epitopes of TOSV Gn glycoproteins by neutralizing mAbs using synthetic peptide arrays on membrane support (SPOT synthesis). These epitopes, separated in primary structure, might be exposed near one another as a conformational epitope in their native structure. In vivo studies were conducted to evaluate the humoral response elicited in mice immunized with the identified peptides. The results underlined the hypothesis that the first two peptides located in the NH2 terminus could form a conformational epitope, while the third, located near the transmembrane sequence in the carboxyl terminus, was necessary to strengthen neutralizing activity. Our results emphasize the importance of identifying neutralizing epitopes shared among the various phleboviruses, which could be exploited for the development of a potential epitope-based diagnostic assay or a polyvalent protective vaccine against different phleboviruses.
Claudia Gandolfo; Shibily Prathyumn; Chiara Terrosi; Gabriele Anichini; Gianni Gori Savellini; Davide Corti; Luisa Bracci; Antonio Lanzavecchia; Gleyder Roman-Sosa; Maria Grazia Cusi. Identification of a Neutralizing Epitope on TOSV Gn Glycoprotein. Vaccines 2021, 9, 924 .
AMA StyleClaudia Gandolfo, Shibily Prathyumn, Chiara Terrosi, Gabriele Anichini, Gianni Gori Savellini, Davide Corti, Luisa Bracci, Antonio Lanzavecchia, Gleyder Roman-Sosa, Maria Grazia Cusi. Identification of a Neutralizing Epitope on TOSV Gn Glycoprotein. Vaccines. 2021; 9 (8):924.
Chicago/Turabian StyleClaudia Gandolfo; Shibily Prathyumn; Chiara Terrosi; Gabriele Anichini; Gianni Gori Savellini; Davide Corti; Luisa Bracci; Antonio Lanzavecchia; Gleyder Roman-Sosa; Maria Grazia Cusi. 2021. "Identification of a Neutralizing Epitope on TOSV Gn Glycoprotein." Vaccines 9, no. 8: 924.
A weak production of INF-β along with an exacerbated release of pro-inflammatory cytokines have been reported during infection by the novel SARS-CoV-2 virus. SARS-CoV-2 encodes several proteins able to counteract the host immune system, which is believed to be one of the most important features contributing to the viral pathogenesis and development of a severe clinical picture. Previous reports have demonstrated that SARS-CoV-2 N protein, along with some non-structural and accessory proteins, efficiently suppresses INF-β production by interacting with RIG-I, an important pattern recognition receptor (PRR) involved in the recognition of pathogen-derived molecules. In the present study, we better characterized the mechanism by which the SARS-CoV-2 N counteracts INF-β secretion and affects RIG-I signaling pathways. In detail, when the N protein was ectopically expressed, we noted a marked decrease in TRIM25-mediated RIG-I activation. The capability of the N protein to bind to, and probably mask, TRIM25 could be the consequence of its antagonistic activity. Furthermore, this interaction occurred at the SPRY domain of TRIM25, harboring the RNA-binding activity necessary for TRIM25 self-activation. Here, we describe new findings regarding the interplay between SARS-CoV-2 and the IFN system, filling some gaps for a better understanding of the molecular mechanisms affecting the innate immune response in COVID-19.
Gianni Gori Savellini; Gabriele Anichini; Claudia Gandolfo; Maria Cusi. SARS-CoV-2 N Protein Targets TRIM25-Mediated RIG-I Activation to Suppress Innate Immunity. Viruses 2021, 13, 1439 .
AMA StyleGianni Gori Savellini, Gabriele Anichini, Claudia Gandolfo, Maria Cusi. SARS-CoV-2 N Protein Targets TRIM25-Mediated RIG-I Activation to Suppress Innate Immunity. Viruses. 2021; 13 (8):1439.
Chicago/Turabian StyleGianni Gori Savellini; Gabriele Anichini; Claudia Gandolfo; Maria Cusi. 2021. "SARS-CoV-2 N Protein Targets TRIM25-Mediated RIG-I Activation to Suppress Innate Immunity." Viruses 13, no. 8: 1439.
Due to their increased transmissibility, three variants of high concern have emerged in the United Kingdom (also known as B.1.1.7 lineage or VOC-202012/01), South Africa (B.1.351 lineage), and Brazil (P1 lineage) with multiple substitutions in the spike protein. Since neutralizing antibodies elicited by vaccination are likely considered as correlates of protection for SARS-CoV-2 infection, it is important to analyze whether vaccinees with mRNA BNT162b2 are equally protected against these emerging SARS-CoV-2 variants. To this aim, we enrolled healthy subjects one month after complete vaccination with Comirnaty and evaluated the neutralizing response against the native Wuhan strain and the emerging B.1.1.7, B.1.351 and P1 lineages, by using the microneutralization assay, currently considered the gold standard test for the evaluation and detection of functional neutralizing antibodies. The most remarkable finding of this study was the significantly lower neutralizing antibody titer against B.1.351 lineage, compared to the wild-type virus. No significant differences were observed with the other two lineages. These findings provide evidence that vaccinated subjects may not be equally protected against all SARS-CoV-2 lineages.
Gabriele Anichini; Chiara Terrosi; Gianni Gori Savellini; Claudia Gandolfo; Federico Franchi; Maria Cusi. Neutralizing Antibody Response of Vaccinees to SARS-CoV-2 Variants. Vaccines 2021, 9, 517 .
AMA StyleGabriele Anichini, Chiara Terrosi, Gianni Gori Savellini, Claudia Gandolfo, Federico Franchi, Maria Cusi. Neutralizing Antibody Response of Vaccinees to SARS-CoV-2 Variants. Vaccines. 2021; 9 (5):517.
Chicago/Turabian StyleGabriele Anichini; Chiara Terrosi; Gianni Gori Savellini; Claudia Gandolfo; Federico Franchi; Maria Cusi. 2021. "Neutralizing Antibody Response of Vaccinees to SARS-CoV-2 Variants." Vaccines 9, no. 5: 517.
The non-structural protein NSs of the Phenuiviridae family members appears to have a role in the host immunity escape. The stability of Toscana virus (TOSV) NSs protein was tested by a cycloheximide (CHX) chase approach on cells transfected with NSs deleted versions fused to a reporter gene. The presence of intrinsically disordered regions (IDRs) both at the C- and N-terminus appeared to affect the protein stability. Indeed, the NSsΔC and NSsΔN proteins were more stable than the wild-type NSs counterpart. Since TOSV NSs exerts its inhibitory function by triggering RIG-I for proteasomal degradation, the interaction of the ubiquitin system and TOSV NSs was further examined. Chase experiments with CHX and the proteasome inhibitor MG-132 demonstrated the involvement of the ubiquitin-proteasome system in controlling NSs protein amount expressed in the cells. The analysis of TOSV NSs by mass spectrometry allowed the direct identification of K104, K109, K154, K180, K244, K294, and K298 residues targeted for ubiquitination. Analysis of NSs K-mutants confirmed the presence and the important role of lysine residues located in the central and the C-terminal parts of the protein in controlling the NSs cellular level. Therefore, we directly demonstrated a new cellular pathway involved in controlling TOSV NSs fate and activity, and this opens the way to new investigations among more pathogenic viruses of the Phenuiviridae family.
Gianni Gori Savellini; Luca Bini; Assunta Gagliardi; Gabriele Anichini; Claudia Gandolfo; Shibily Prathyumnan; Maria Cusi. Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation. Viruses 2020, 12, 1153 .
AMA StyleGianni Gori Savellini, Luca Bini, Assunta Gagliardi, Gabriele Anichini, Claudia Gandolfo, Shibily Prathyumnan, Maria Cusi. Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation. Viruses. 2020; 12 (10):1153.
Chicago/Turabian StyleGianni Gori Savellini; Luca Bini; Assunta Gagliardi; Gabriele Anichini; Claudia Gandolfo; Shibily Prathyumnan; Maria Cusi. 2020. "Ubiquitin and Not Only Unfolded Domains Drives Toscana Virus Non-Structural NSs Protein Degradation." Viruses 12, no. 10: 1153.
Toscana virus (TOSV) is a Phlebovirus transmitted to humans by phlebotomines and represent an etiological agent of acute aseptic meningitis (AAM) in countries where the virus is endemic, including Italy. Incidence of TOSV infections is closely associated with the geographical distribution of the phlebotomine vectors which in turn is affected by climate changes that determine survival and spread. As a result, TOSV infections show a seasonal trend with a peak of incidence in summer months. To measure the prevalence of TOSV infections in AAM patients in central Italy and evaluate the climate changes in phlebotomine vectors ecology and virus propagation. One thousand and seventy-three cerebrospinal fluid samples (CSFs), collected from patients with suspected viral meningitis, were collected over nine years (2011-2019) during the May to October period and tested for viruses most commonly associated with AAM. Serum samples addressed to the Microbiology and Virology Unit of “S. Maria delle Scotte” Hospital for confirmation acute TOSV infection (n = 324) were tested for TOSV-specific IgM and IgG. Among the CSF samples, 1.3% were positive for Enteroviruses; 0.9% for Varicella zoster virus, 1.9% for Herpes simplex virus type-1/2 and 4.6% for TOSV. Serum IgM analyses disclosed TOSV-specific IgM in 27.1% of sera suggesting the predominant involvement of TOSV in neuroinvasive infections. This data confirms the predominant role of TOSV as causative agent of AAM during the summer time in endemic countries. Moreover, climate changes affecting phlebotomine vectors persistence, reproduction and activity could be involved in the cyclic nature of TOSV infection reported during the last nine years.
Gianni Gori Savellini; Claudia Gandolfo; Maria Grazia Cusi. Epidemiology of Toscana virus in South Tuscany over the years 2011-2019. Journal of Clinical Virology 2020, 128, 104452 .
AMA StyleGianni Gori Savellini, Claudia Gandolfo, Maria Grazia Cusi. Epidemiology of Toscana virus in South Tuscany over the years 2011-2019. Journal of Clinical Virology. 2020; 128 ():104452.
Chicago/Turabian StyleGianni Gori Savellini; Claudia Gandolfo; Maria Grazia Cusi. 2020. "Epidemiology of Toscana virus in South Tuscany over the years 2011-2019." Journal of Clinical Virology 128, no. : 104452.
An increase in measles cases worldwide, with outbreaks, has been registered in the last few years, despite the availability of a safe and highly efficacious vaccine. In addition to an inadequate vaccination coverage, even in high-income European countries studies proved that some vaccinated people were also found seronegative years after vaccination, thus increasing the number of people susceptible to measles infection. In this study, we evaluated the immunization status and the seroprevalence of measles antibodies among 1092 healthy adults, either vaccinated or naturally infected, in order to investigate the persistence of anti-measles IgG. Among subjects who received two doses of measles vaccine, the neutralizing antibody titer tended to decline over time. In addition, data collected from a neutralization assay performed on 110 healthy vaccinated subjects suggested an inverse correlation between neutralizing antibody titers and the time elapsed between the two vaccinations, with a significant decline in the neutralizing titer when the interval between the two doses was ≥11 years. On the basis of these results, monitoring the serological status of the population 10–12 years after vaccination could be important both to limit the number of people who are potentially susceptible to measles, despite the high efficacy of MMR vaccine, and to recommend a booster vaccine for the seronegatives.
Gabriele Anichini; Claudia Gandolfo; Simonetta Fabrizi; Giovan Battista Miceli; Chiara Terrosi; Gianni Gori Savellini; Shibily Prathyumnan; Daniela Orsi; Giuseppe Battista; Maria Grazia Cusi. Seroprevalence to Measles Virus after Vaccination or Natural Infection in an Adult Population, in Italy. Vaccines 2020, 8, 66 .
AMA StyleGabriele Anichini, Claudia Gandolfo, Simonetta Fabrizi, Giovan Battista Miceli, Chiara Terrosi, Gianni Gori Savellini, Shibily Prathyumnan, Daniela Orsi, Giuseppe Battista, Maria Grazia Cusi. Seroprevalence to Measles Virus after Vaccination or Natural Infection in an Adult Population, in Italy. Vaccines. 2020; 8 (1):66.
Chicago/Turabian StyleGabriele Anichini; Claudia Gandolfo; Simonetta Fabrizi; Giovan Battista Miceli; Chiara Terrosi; Gianni Gori Savellini; Shibily Prathyumnan; Daniela Orsi; Giuseppe Battista; Maria Grazia Cusi. 2020. "Seroprevalence to Measles Virus after Vaccination or Natural Infection in an Adult Population, in Italy." Vaccines 8, no. 1: 66.
It is known that the non-structural protein (NSs) of Toscana virus (TOSV), an emergent sandfly-borne virus causing meningitis or more severe central nervous system injuries in humans, exerts its function triggering RIG-I for degradation in a proteasome-dependent manner, thus breaking off the IFN-β production. The non-structural protein of different members of Bunyavirales has recently appeared as a fundamental protagonist in immunity evasion through ubiquitination-mediated protein degradation targets. We showed that TOSV NSs has an E3 ubiquitin ligase activity, mapping at the carboxy-terminal domain and also involving the amino-terminal of the protein. Indeed, neither the amino- (NSsΔN) nor the carboxy- (NSsΔC) terminal-deleted mutants of TOSV NSs were able to cause ubiquitin-mediated proteasome degradation of RIG-I. Moreover, the addition of the C-terminus of TOSV NSs to the homologous protein of the Sandfly Fever Naples Virus, belonging to the same genus and unable to inhibit IFN-β activity, conferred new properties to this protein, favoring RIG-I ubiquitination and its degradation. NSs lost its antagonistic activity to IFN when one of the terminal residues was missing. Therefore, we showed that NSs could behave as an atypical RING between RING (RBR) E3 ubiquitin ligases. This is the first report which identified the E3 ubiquitin ligase activity in a viral protein among negative strand RNA viruses. Toscana virus is an emergent sandfly-borne virus mainly transmitted to humans by phlebotomine sandflies, which can cause meningitis or more severe central nervous system injuries in some subjects. As many other RNA viruses, it counteracts IFN-β expression by its non-structural protein. Our results expanded our knowledge about the molecular mechanisms by which TOSV exerts its activity as an E3 ubiquitin ligase. This is the first example of a viral protein presenting this activity among negative-strand RNA viruses. Thus, the recognition of this activity and its substrates among viruses are of primary importance to understand how viruses can alter their fitness by the ubiquitin pathway and provide an attractive target for the development of antiviral therapies.
Gianni Gori Savellini; Gabriele Anichini; Claudia Gandolfo; Shibily Prathyumnan; Maria Grazia Cusi. Toscana virus non-structural protein NSs acts as E3 ubiquitin ligase promoting RIG-I degradation. PLOS Pathogens 2019, 15, e1008186 .
AMA StyleGianni Gori Savellini, Gabriele Anichini, Claudia Gandolfo, Shibily Prathyumnan, Maria Grazia Cusi. Toscana virus non-structural protein NSs acts as E3 ubiquitin ligase promoting RIG-I degradation. PLOS Pathogens. 2019; 15 (12):e1008186.
Chicago/Turabian StyleGianni Gori Savellini; Gabriele Anichini; Claudia Gandolfo; Shibily Prathyumnan; Maria Grazia Cusi. 2019. "Toscana virus non-structural protein NSs acts as E3 ubiquitin ligase promoting RIG-I degradation." PLOS Pathogens 15, no. 12: e1008186.
All available sequences of the three genome segments of Toscana virus with date and location of sampling were analysed using Bayesian phylodynamic methods. We estimate that extant Toscana virus strains had a common ancestor in the late 16th to early 17th century AD, in territories controlled by the Ottoman Empire, giving rise to an ancestral genotype A/B in north Africa and to genotype C in the Balkans. Subsequent spread into western Europe may have occurred during the period of European colonization of north Africa in the 19th and early 20th centuries AD, establishing genotypes A and B in Italy and Spain respectively. Very little positive evolutionary selection pressure is detectable in Toscana virus, suggesting that the virus has become well adapted to its human hosts. There is also no convincing evidence of reassortment between genome segments, despite genotypes A and B now co-circulating in several countries.
Maria Grazia Cusi; Claudia Gandolfo; Gianni Gori Savellini; Chiara Terrosi; Rebecca A. Sadler; Derek Gatherer. Phylodynamic analysis of the historical spread of Toscana virus around the Mediterranean. 2018, 380477 .
AMA StyleMaria Grazia Cusi, Claudia Gandolfo, Gianni Gori Savellini, Chiara Terrosi, Rebecca A. Sadler, Derek Gatherer. Phylodynamic analysis of the historical spread of Toscana virus around the Mediterranean. . 2018; ():380477.
Chicago/Turabian StyleMaria Grazia Cusi; Claudia Gandolfo; Gianni Gori Savellini; Chiara Terrosi; Rebecca A. Sadler; Derek Gatherer. 2018. "Phylodynamic analysis of the historical spread of Toscana virus around the Mediterranean." , no. : 380477.
Respiratory syncytial virus (RSV) is a major cause of severe respiratory infections in children and elderly people, and no marketed vaccine exists. In this study, we generated and analyzed a subunit vaccine against RSV based on a novel genome replication-deficient Sendai virus (SeV) vector. We inserted the RSV F protein, known to be a genetically stable antigen, into our vector in a specific way to optimize the vaccine features. By exchanging the ectodomain of the SeV F protein for its counterpart from RSV, we created a chimeric vectored vaccine that contains the RSV F protein as an essential structural component. In this way, the antigen is actively expressed on the surfaces of vaccine particles in its prefusion conformation, and as recently reported for other vectored vaccines, the occurrence of silencing mutations of the transgene in the vaccine genome can be prevented. In addition, its active gene expression contributes to further stimulation of the immune response. In order to understand the best route of immunization, we compared vaccine efficacies after intranasal (i.n.) or intramuscular (i.m.) immunization of BALB/c mice. Via both routes, substantial RSV-specific immune responses were induced, consisting of serum IgG and neutralizing antibodies, as well as cytotoxic T cells. Moreover, i.n. immunization was also able to stimulate specific mucosal IgA in the upper and lower respiratory tract. In virus challenge experiments, animals were protected against RSV infection after both i.n. and i.m. immunization without inducing vaccine-enhanced disease. Above all, the replication-deficient SeV appeared to be safe and well tolerated. IMPORTANCE Respiratory syncytial virus (RSV) is a major cause of respiratory diseases in young children and elderly people worldwide. There is a great demand for a licensed vaccine. Promising existing vaccine approaches based on live-attenuated vaccines or viral vectors have suffered from unforeseen drawbacks related to immunogenicity and attenuation. We provide a novel RSV vaccine concept based on a genome replication-deficient Sendai vector that has many favorable vaccine characteristics. The specific vaccine design guarantees genetic stability of the transgene; furthermore, it supports a favorable presentation of the antigen, activating the adaptive response, features that other vectored vaccine approaches have often had difficulties with. Wide immunological and pathological analyses in mice confirmed the validity and efficacy of this approach after both parenteral and mucosal administration. Above all, this concept is suitable for initiating clinical studies, and it could also be applied to other infectious diseases.
Marian Alexander Wiegand; Gianni Gori-Savellini; Claudia Gandolfo; Guido Papa; Christine Kaufmann; Eva Felder; Alessandro Ginori; Maria Giulia Disanto; Donatella Spina; Maria Grazia Cusi. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease. Journal of Virology 2017, 91, e02298-16 .
AMA StyleMarian Alexander Wiegand, Gianni Gori-Savellini, Claudia Gandolfo, Guido Papa, Christine Kaufmann, Eva Felder, Alessandro Ginori, Maria Giulia Disanto, Donatella Spina, Maria Grazia Cusi. A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease. Journal of Virology. 2017; 91 (10):e02298-16.
Chicago/Turabian StyleMarian Alexander Wiegand; Gianni Gori-Savellini; Claudia Gandolfo; Guido Papa; Christine Kaufmann; Eva Felder; Alessandro Ginori; Maria Giulia Disanto; Donatella Spina; Maria Grazia Cusi. 2017. "A Respiratory Syncytial Virus Vaccine Vectored by a Stable Chimeric and Replication-Deficient Sendai Virus Protects Mice without Inducing Enhanced Disease." Journal of Virology 91, no. 10: e02298-16.
Toscana Virus (TOSV) is a Phlebovirus responsible for central nervous system (CNS) injury in humans. The TOSV non-structural protein (NSs), which interacting with RIG-I leads to its degradation, was analysed in the C terminus fragment in order to identify its functional domains. To this aim, two C-terminal truncated NSs proteins, Δ1C-NSs (aa 1-284) and Δ2C-NSs (aa 1-287) were tested. Only Δ1C-NSs did not present any inhibitory effect on RIG-I and it showed a greater stability than the whole NSs protein. Moreover, the deletion of the TLQ aa sequence interposed between the two ΔC constructs caused a greater accumulation of the protein with a weak inhibitory effect on RIG-I, indicating some involvement of these amino acids in the NSs activity. Nevertheless, all the truncated proteins were still able to interact with RIG-I, suggesting that the domains responsible for RIG-I signaling and RIG-I interaction are mapped on different regions of the protein
Gianni Gori Savellini; Claudia Gandolfo; Maria Grazia Cusi. Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability. Virology 2015, 486, 255 -262.
AMA StyleGianni Gori Savellini, Claudia Gandolfo, Maria Grazia Cusi. Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability. Virology. 2015; 486 ():255-262.
Chicago/Turabian StyleGianni Gori Savellini; Claudia Gandolfo; Maria Grazia Cusi. 2015. "Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability." Virology 486, no. : 255-262.
Toscana virus (TOSV) is a Phlebovirus responsible for human neurological infections in endemic Mediterranean areas. The main viral target is the central nervous system, with viremia as a way of dissemination throughout the host. This study was aimed at understanding the spread of TOSV in the host by identifying the cell population infected by the virus and the vehicle to the organs. In vivo studies provided evidence that endothelial cells are infected by TOSV, indicating their potential role in the diffusion of the virus following viremic spread. These results were further confirmed in vitro. Human peripheral mononuclear blood cells were infected with TOSV; only monocyte-derived dendritic cells were identified as susceptible to TOSV infection. Productive viral replication was then observed in human monocyte-derived dendritic cells (moDCs) and in human endothelial cells by recovery of the virus from a cell supernatant. Interleukin-6 was produced by both cell types upon TOSV infection, mostly by endothelial cells, while moDCs particularly expressed TNF-α, which is known to induce a long-lasting decrease in endothelial cell barrier function. These cells could therefore be implicated in the spread of the virus in the host and in the infection of tissues that are affected by the disease, such as the central nervous system. The identification of in vitro and in vivo TOSV cell targets is an important tool for understanding the pathogenesis of the infection, providing new insight into virus–cell interaction for improved knowledge and control of this viral disease.
Maria Grazia Cusi; Claudia Gandolfo; Chiara Terrosi; Gianni Gori Savellini; Giuseppe Belmonte; Clelia Miracco. Toscana virus infects dendritic and endothelial cells opening the way for the central nervous system. Journal of NeuroVirology 2015, 22, 307 -315.
AMA StyleMaria Grazia Cusi, Claudia Gandolfo, Chiara Terrosi, Gianni Gori Savellini, Giuseppe Belmonte, Clelia Miracco. Toscana virus infects dendritic and endothelial cells opening the way for the central nervous system. Journal of NeuroVirology. 2015; 22 (3):307-315.
Chicago/Turabian StyleMaria Grazia Cusi; Claudia Gandolfo; Chiara Terrosi; Gianni Gori Savellini; Giuseppe Belmonte; Clelia Miracco. 2015. "Toscana virus infects dendritic and endothelial cells opening the way for the central nervous system." Journal of NeuroVirology 22, no. 3: 307-315.
Our aim is to detect the infection by Toscana virus (TOSV) and other Phleboviruses in the sera and cerebro-spinal fluid (CSF) of patients with meningitis in Tunisia. We examined various species of phlebotomus present in Tunisia to determine whether or not a direct relationship exists between cases of meningitis and the viruses circulating in the insect vectors. Patients with the meningeal syndrome were tested for anti-TOSV IgM and IgG using an indirect Enzyme-Linked Immunosorbent Assay (ELISA) and for the presence of TOSV and other Phleboviruses using a RT-PCR test. An entomological study was carried out using CDC light traps to trap sandflies in different bioclimatic zones of Tunisia. Collected sandflies were tested by RT-PCR for the presence of TOSV and other Phleboviruses and subsequently by viral isolation on Vero cells. Of 263 patients were tested using ELISA of which 12.16% (n = 32/263) were IgM positive for anti TOSV. Of these 32 patients, 78% (n = 25/32) were IgG positive. 12.86% (n = 18/140) of the CSF samples tested by RT-PCR were positive for the Toscana virus. One CSF sample tested by RT-PCR revealed the presence of Sandfly Fever Sicilian Virus (SFSV). The Punique virus was identified in one sandfly pool. This study confirms, for the first time, that TOSV is involved in a neurological disorder in North Africa. The incidence of this involvement in Tunisia conforms with observations made in other Mediterranean countries. Moreover, for the first time, a molecular approach was used to detect SFSV in a Tunisian patient displaying neurological symptoms.
Ons Fezaa; Youmna M’Ghirbi; Gianni Gori Savellini; Lamia Ammari; Nahed Hogga; Henda Triki; Maria Grazia Cusi; Ali Bouattour. Serological and molecular detection of Toscana and other Phleboviruses in patients and sandflies in Tunisia. BMC Infectious Diseases 2014, 14, 598 -598.
AMA StyleOns Fezaa, Youmna M’Ghirbi, Gianni Gori Savellini, Lamia Ammari, Nahed Hogga, Henda Triki, Maria Grazia Cusi, Ali Bouattour. Serological and molecular detection of Toscana and other Phleboviruses in patients and sandflies in Tunisia. BMC Infectious Diseases. 2014; 14 (1):598-598.
Chicago/Turabian StyleOns Fezaa; Youmna M’Ghirbi; Gianni Gori Savellini; Lamia Ammari; Nahed Hogga; Henda Triki; Maria Grazia Cusi; Ali Bouattour. 2014. "Serological and molecular detection of Toscana and other Phleboviruses in patients and sandflies in Tunisia." BMC Infectious Diseases 14, no. 1: 598-598.
Marian Wiegand; Gianni Gori-Savellini; Barbara Martorelli; Sascha Bossow; Wolfgang J. Neubert; Maria Grazia Cusi. Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. Vaccine 2013, 31, 3888 -3893.
AMA StyleMarian Wiegand, Gianni Gori-Savellini, Barbara Martorelli, Sascha Bossow, Wolfgang J. Neubert, Maria Grazia Cusi. Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector. Vaccine. 2013; 31 (37):3888-3893.
Chicago/Turabian StyleMarian Wiegand; Gianni Gori-Savellini; Barbara Martorelli; Sascha Bossow; Wolfgang J. Neubert; Maria Grazia Cusi. 2013. "Evaluation of a novel immunogenic vaccine platform based on a genome replication-deficient Sendai vector." Vaccine 31, no. 37: 3888-3893.
Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-β) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92: 71–79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-β promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-β promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response.
Gianni Gori-Savellini; Melissa Valentini; Maria Grazia Cusi. Toscana Virus NSs Protein Inhibits the Induction of Type I Interferon by Interacting with RIG-I. Journal of Virology 2013, 87, 6660 -6667.
AMA StyleGianni Gori-Savellini, Melissa Valentini, Maria Grazia Cusi. Toscana Virus NSs Protein Inhibits the Induction of Type I Interferon by Interacting with RIG-I. Journal of Virology. 2013; 87 (12):6660-6667.
Chicago/Turabian StyleGianni Gori-Savellini; Melissa Valentini; Maria Grazia Cusi. 2013. "Toscana Virus NSs Protein Inhibits the Induction of Type I Interferon by Interacting with RIG-I." Journal of Virology 87, no. 12: 6660-6667.
Toscana virus is the main phlebovirus circulating in Tuscany during the warm season, thus, a seroprevalence study was performed in the same area to estimate the antibody prevalence rates for sandfly fever Sicilian virus (SFSV) that is endemic in the Mediterranean countries. The low seroprevalence observed in this study shows that this virus does not play an important role in the etiology of febrile illness in central Italy.
Maria Grazia Cusi; Claudia Gandolfo; Melissa Valentini; Gianni Gori Savellini. Seroprevalence of Antibodies to Sandfly Fever Sicilian Virus in a Sample Population in Tuscany, Italy. Vector-Borne and Zoonotic Diseases 2013, 13, 345 -346.
AMA StyleMaria Grazia Cusi, Claudia Gandolfo, Melissa Valentini, Gianni Gori Savellini. Seroprevalence of Antibodies to Sandfly Fever Sicilian Virus in a Sample Population in Tuscany, Italy. Vector-Borne and Zoonotic Diseases. 2013; 13 (5):345-346.
Chicago/Turabian StyleMaria Grazia Cusi; Claudia Gandolfo; Melissa Valentini; Gianni Gori Savellini. 2013. "Seroprevalence of Antibodies to Sandfly Fever Sicilian Virus in a Sample Population in Tuscany, Italy." Vector-Borne and Zoonotic Diseases 13, no. 5: 345-346.
High intrathecal levels of anti-myelin basic protein (MBP) IgM were previously found to be significantly associated with early favorable course in a cohort of patients with multiple sclerosis (MS). A mAb to MBP 105-120 recognizing the 222-228 epitope of the extracellular domain of high affinity immunoglobulin gamma Fc-receptor I (CD64) was isolated from EBV(+) B cell clones of long-term stable RRMS patients. This mAb exerted immunosuppressive activity on MS-derived T cell lines through induction and release of high amounts of interleukin-10 and decreased levels of interleukin-12 from activated monocytes providing the biological basis for a potential new treatment for MS and other immune-mediated neurological disorders
P. Annunziata; C. Cioni; L. Cantalupo; G. Di Genova; Gianni Gori Savellini; G. Cusi. Immunosuppressive monoclonal antibody to CD64 from patients with long-term stable multiple sclerosis. Journal of Neuroimmunology 2013, 256, 62 -70.
AMA StyleP. Annunziata, C. Cioni, L. Cantalupo, G. Di Genova, Gianni Gori Savellini, G. Cusi. Immunosuppressive monoclonal antibody to CD64 from patients with long-term stable multiple sclerosis. Journal of Neuroimmunology. 2013; 256 (1-2):62-70.
Chicago/Turabian StyleP. Annunziata; C. Cioni; L. Cantalupo; G. Di Genova; Gianni Gori Savellini; G. Cusi. 2013. "Immunosuppressive monoclonal antibody to CD64 from patients with long-term stable multiple sclerosis." Journal of Neuroimmunology 256, no. 1-2: 62-70.
Toscana virus (TOSV) is an arthropod-borne virus, transmitted to humans by Phlebotomus spp. Sandflies, which causes neurological diseases such as aseptic meningitis and meningoencephalitis. The commercial enzyme-linked immunosorbent assay (ELISA) is used widely to detect anti-TOSV IgG and IgM antibodies and to allow for rapid diagnosis of infection (Diesse Diagnostica Senese, Siena, Italy). Recently, an immunochromatographic assay (ICA) was developed for human anti-TOSV IgG or IgM detection by InBios International (Seattle, WA, USA). A comparison of the two diagnostic assays was performed on one hundred serum samples collected from patients hospitalized with suspected TOSV meningitis. Both assays were in excellent agreement, for both IgG and IgM detection. For IgM, 64/65 ELISA positive samples were positive by ICA. One serum, positive for specific IgM by ELISA but negative by ICA, was confirmed by direct diagnosis, with TOSV RNA detection in the patient's cerebrospinal fluid by PCR. For IgG, 64 samples were positive by ICA out of 71 ELISA positive samples. The discordant sera were positive by immunofluorescence and neutralization tests. Three out of these seven samples were also positive by IgM ICA. The sensitivity of these new assays compared to ELISA, which is used routinely, was 98.5% for IgM and 90.1% for IgG, while specificity was 100% in both cases. This data shows that ICA could be a reliable alternative test for serological diagnosis of TOSV infection in humans.
Raymond Houghton; Gianni Gori Savellini; Hongjing Chen; Yvonne Stevens; Jennifer Moon; Stan Morkowski; Syamal Raychaudhuri; Melissa Valentini; Maria Grazia Cusi. Comparison of a new prototype immunochromatographic assay and a commercial enzyme-linked immunosorbent assay for the detection of serum antibodies against Toscana virus. Journal of Virological Methods 2013, 187, 182 -184.
AMA StyleRaymond Houghton, Gianni Gori Savellini, Hongjing Chen, Yvonne Stevens, Jennifer Moon, Stan Morkowski, Syamal Raychaudhuri, Melissa Valentini, Maria Grazia Cusi. Comparison of a new prototype immunochromatographic assay and a commercial enzyme-linked immunosorbent assay for the detection of serum antibodies against Toscana virus. Journal of Virological Methods. 2013; 187 (1):182-184.
Chicago/Turabian StyleRaymond Houghton; Gianni Gori Savellini; Hongjing Chen; Yvonne Stevens; Jennifer Moon; Stan Morkowski; Syamal Raychaudhuri; Melissa Valentini; Maria Grazia Cusi. 2013. "Comparison of a new prototype immunochromatographic assay and a commercial enzyme-linked immunosorbent assay for the detection of serum antibodies against Toscana virus." Journal of Virological Methods 187, no. 1: 182-184.
SummaryObjectivesHigh Toscana virus (TOSV) antibody seropositivity rates have been documented in the last decade, especially in the Mediterranean area. It is unclear if these rates are associated with a recent or past exposure to the virus. This is of importance, as primary infection can cause neurologic complications, especially in adults. The aim of the present study was to assess the current active TOSV circulation in western Sicily.MethodsA cross-sectional seroprevalence study was conducted on 271 individuals aged 4–92 years, sampled from the general population of a small city. Each participant completed a self-administered questionnaire and provided serum, which was analyzed for the presence of specific anti-TOSV IgM and IgG.ResultsAnti-TOSV IgM was detected in eight (3.0%) participants, of whom only three had anti-TOSV IgG. The prevalence of anti-TOSV IgM was highest in subjects aged 25–34 and 35–44 years (7.1% and 4.8%, respectively). All subjects positive for anti-TOSV IgM were resident in the suburban area.ConclusionsThe detection of IgM documented the circulation of TOSV, a Phlebovirus, in a random population sample of Sicilian adults. The highest risk of TOSV seroconversion in subjects living in the suburbs appears to suggest a high density of TOSV vectors in peri-urban areas.
Emanuele Amodio; Maria Grazia Cusi; Rosalia Maria Valenti; Melissa Valentini; Caterina Mammina; Gianni Gori Savellini; Francesco Vitale; Nino Romano; James J. Goedert; Giuseppe Calamusa. Immunoglobulin M seropositivity for Toscana virus in a random population sample in Sicily. International Journal of Infectious Diseases 2012, 16, e633 -e635.
AMA StyleEmanuele Amodio, Maria Grazia Cusi, Rosalia Maria Valenti, Melissa Valentini, Caterina Mammina, Gianni Gori Savellini, Francesco Vitale, Nino Romano, James J. Goedert, Giuseppe Calamusa. Immunoglobulin M seropositivity for Toscana virus in a random population sample in Sicily. International Journal of Infectious Diseases. 2012; 16 (8):e633-e635.
Chicago/Turabian StyleEmanuele Amodio; Maria Grazia Cusi; Rosalia Maria Valenti; Melissa Valentini; Caterina Mammina; Gianni Gori Savellini; Francesco Vitale; Nino Romano; James J. Goedert; Giuseppe Calamusa. 2012. "Immunoglobulin M seropositivity for Toscana virus in a random population sample in Sicily." International Journal of Infectious Diseases 16, no. 8: e633-e635.
E13098 Background: TSPP is a poly-epitope peptide anticancer vaccine able to generate a thymidylate syntase (TS) specific T cell response with antitumor activity in preclinical models, expecially when used in sequential combination with 5-FU. TS is in fact involved in DNA replication and is the major pharmacological target of fluoropyrimidines whose activity leads in turn to TS upregulation. On these basis we designed a phase Ib trial where we investigated the safety and the immunobiological activity of TSPP + GOLFIG (Gemcitabine + FOLFOX-4 + GM-CSF + IL-2) regimen. Methods: TSPP/VAC-1 (Eudract 2009-016897-33) is a monocentric dose finding Phase Ib trial. 12 pretreated metastatic colon cancer patients were enrolled between April and November 2011. All of them received biochemotherapy according to the GOLFIG regimen biweekly and TSPP (on day 7) diluted in motanide ISA720 (1:1) at the dosage of 100 (3 patients), 200 (3 patients) and 300 ug (6 patients). Results: No life-threatening adverse events were observed. Grade 3 leucopenia (2 cases), thrombocitopenia (3 cases), anemia (3 cases), nausea/vomiting (2 cases), and dyarrhea (4 cases) along with 3 cases of oxaliplatin reaction were recorded. Fever and flu-like symptoms were common along cytokine administration. An IFN-gamma ELISPOT assay recorded an increase in TS specific CTL precursors in 3/6 evaluable patients; it was also observed an increase in lymphocytes, eosinophils, terminal effector memory and central memory T cells and in both c-ANCA and p-ANCA (P= 0.02) in the peripheral blood and a significant reduction in inflammatory markers (LDH, CRP and ESR). Quality of life analysis revealed a general improvement in patients’health state along the treatment. 1 partial response, 6 disease stabilizations and 2 progessions of disease were recorded. TSPP Maximal Tolerated Dose was not reached, while the Optimal Biological Dose was identified at 300 ug. Conclusions: Our results suggest that the GOLFIG + TSPP vaccine combination is safe and immunologically active and deserves to be evaluated in a further phase II trial.
Pierpaolo Correale; Pierpaolo Pastina; Cirino Botta; Maria Grazia Rossetti; Serena Apollinari; Elena Bestoso; Antonella Fioravanti; Giacomo Guidelli; Federico Chellini; Giovanni Mantovani; Gianni Gori Savellini; Salvatore Francesco Carbone; Veronica Ricci; Assunta Basile; Marco Pagliuchi; Pierosandro Tagliaferri; Luigi Pirtoli; Maria Grazia Cusi. Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmuno-burst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial. Journal of Clinical Oncology 2012, 30, e13098 -e13098.
AMA StylePierpaolo Correale, Pierpaolo Pastina, Cirino Botta, Maria Grazia Rossetti, Serena Apollinari, Elena Bestoso, Antonella Fioravanti, Giacomo Guidelli, Federico Chellini, Giovanni Mantovani, Gianni Gori Savellini, Salvatore Francesco Carbone, Veronica Ricci, Assunta Basile, Marco Pagliuchi, Pierosandro Tagliaferri, Luigi Pirtoli, Maria Grazia Cusi. Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmuno-burst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial. Journal of Clinical Oncology. 2012; 30 (15_suppl):e13098-e13098.
Chicago/Turabian StylePierpaolo Correale; Pierpaolo Pastina; Cirino Botta; Maria Grazia Rossetti; Serena Apollinari; Elena Bestoso; Antonella Fioravanti; Giacomo Guidelli; Federico Chellini; Giovanni Mantovani; Gianni Gori Savellini; Salvatore Francesco Carbone; Veronica Ricci; Assunta Basile; Marco Pagliuchi; Pierosandro Tagliaferri; Luigi Pirtoli; Maria Grazia Cusi. 2012. "Phase Ib study of TSPP (thymidilate synthase poly-epitope peptide) vaccine in combination with GOLFIG chemoimmuno-burst in advanced colon cancer patients: Results from the TSPP/VAC-1/c trial." Journal of Clinical Oncology 30, no. 15_suppl: e13098-e13098.
Pierpaolo Correale; Pierpaolo Pastina; Cirino Botta; Serena Apollinari; Elena Bestoso; Antonella Fioravanti; Giacomo Maria Guidelli; Federico Chellini; Maria Grazia Rossetti; Gianni Gori Savellini; Maria Assunta Basile; Marco Pagliuchi; Pierosandro Tagliaferri; Luigi Pirtoli; Maria Grazia Cusi. Abstract LB-229: Treatment of advanced cancer patients with a newest poly-epitope peptide vaccine to the thymidylate synthase(TSPP): a phase Ib (TSPP/VAC1) trial. Clinical Trials 2012, 72, 1 -229.
AMA StylePierpaolo Correale, Pierpaolo Pastina, Cirino Botta, Serena Apollinari, Elena Bestoso, Antonella Fioravanti, Giacomo Maria Guidelli, Federico Chellini, Maria Grazia Rossetti, Gianni Gori Savellini, Maria Assunta Basile, Marco Pagliuchi, Pierosandro Tagliaferri, Luigi Pirtoli, Maria Grazia Cusi. Abstract LB-229: Treatment of advanced cancer patients with a newest poly-epitope peptide vaccine to the thymidylate synthase(TSPP): a phase Ib (TSPP/VAC1) trial. Clinical Trials. 2012; 72 (8):1-229.
Chicago/Turabian StylePierpaolo Correale; Pierpaolo Pastina; Cirino Botta; Serena Apollinari; Elena Bestoso; Antonella Fioravanti; Giacomo Maria Guidelli; Federico Chellini; Maria Grazia Rossetti; Gianni Gori Savellini; Maria Assunta Basile; Marco Pagliuchi; Pierosandro Tagliaferri; Luigi Pirtoli; Maria Grazia Cusi. 2012. "Abstract LB-229: Treatment of advanced cancer patients with a newest poly-epitope peptide vaccine to the thymidylate synthase(TSPP): a phase Ib (TSPP/VAC1) trial." Clinical Trials 72, no. 8: 1-229.