Fausto Baldanti

Policlinico San Matteo Pavia Fondazione IRCCS, Ticinum, Lombardy, Italy

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Publications (258)899.02 Total impact

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    ABSTRACT: The PA protein of Influenza A virus (IAV) encoded by segment 3 acts as a specialized RNA endonuclease in the transcription of the viral genome. The same genomic segment encodes for a second shorter protein, termed PA-X, with the first 191 N-terminal aminoacids (aa) identical to PA, but with a completely different C-ter domain of 61 aa, due to a ribosomal frameshifting. In addition, it has been shown that several IAV isolates encode for a naturally truncated PA-X variant, PAXΔC20, missing the last 20 aa. The biochemical properties of PA-X and PAXΔC20 have been poorly investigated so far. Here, we have carried out an enzymatic characterization of PA-X and its naturally deleted form, in comparison with PA from the human IAV strain A/WSN/33 (H1N1). Our results showed, to the best of our knowledge for the first time, that PA-X possesses an endonucleolytic activity. Both PA and PA-X preferentially cut single stranded RNA regions, but with some differences. In addition, we showed that PAXΔC20 has severely reduced nuclease activity. These results point to a previously undetected role of the last C-ter 20 aa for the catalytic activity of PA-X and support distinct roles for these proteins in the viral life cycle.
    Nucleic Acids Research 09/2015; DOI:10.1093/nar/gkv926 · 9.11 Impact Factor
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    ABSTRACT: Influenza A viruses are characterised by their rapid evolution, and the appearance of point mutations in the viral hemagglutinin (HA) domain causes seasonal epidemics. The A(H3N2) virus has higher mutation rate than the A(H1N1) virus. The aim of this study was to reconstruct the evolutionary dynamics of the A(H3N2) viruses circulating in Italy between 2004 and 2012 in the light of the forces driving viral evolution. Phylodinamic analyses were made using a Bayesian method, and codon-specific positive selection acting on the HA coding sequence was evaluated. Global and local phylogenetic analyses showed that the Italian strains collected between 2004 and 2012 grouped into five significant Italian clades that included viral sequences circulating in different epidemic seasons. The time of the most recent common ancestor (tMRCA) of the tree root was between May and December 2003. The tMRCA estimates of the major clades suggest that the origin of a new viral strain precedes the effective circulation of the strain in the Italian population by 6-31 months, thus supporting a central role of global migration in seeding the epidemics in Italy. The study of selection pressure showed that four codons were under positive selection, three of which were located in antigenic sites. Analysis of population dynamics showed the alternation of periods of exponential growth followed by a decrease in the effective number of infections corresponding to epidemic and inter-epidemic seasons. Our analyses suggest that a complex interaction between the immune status of the population, migrations, and a few selective sweeps drive the influenza A(H3N2) virus evolution. Our findings suggest the possibility of the year-round survival of local strains even in temperate zones, a hypothesis that warrants further investigation.
    PLoS ONE 09/2015; 10(9):e0137099. DOI:10.1371/journal.pone.0137099 · 3.23 Impact Factor
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    ABSTRACT: Since December 2013, chikungunya virus (CHIKV) spread in many countries of the Western Hemisphere, and during the last year some cases of infected European travelers, coming back from the Caribbean, have been reported. The risk of acquiring severe travel-related illness is higher in immunocompromised subjects, such as patient with human immunodeficiency virus (HIV) infection or solid organ transplant recipients. We reported the first case, to our knowledge, of CHIKV infection in an HIV-infected kidney transplant recipient.This article is protected by copyright. All rights reserved.
    Transplant Infectious Disease 09/2015; DOI:10.1111/tid.12453 · 2.06 Impact Factor
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    ABSTRACT: Opportunistic viral infections are still a major complication following solid organ transplantation. Immune monitoring may allow the identification of patients at risk of infection and, eventually, the modulation of immunosuppressive strategies. Immune monitoring can be performed using virus-specific and non virus-specific assays. This article describes and summarizes the pros and cons of the different technical approaches. Among the assays based on non virus-specific antigens, the enumeration of T-cell subsets, the quantification of cytokines and chemokines and the quantification of intracellular adenosine triphosphate following mitogen stimulation are described and their clinical applications to determine the risk for viral infection are discussed. In addition, current specific methods available for monitoring viral-specific T-cell responses are summarized, such as peptide-MHC multimer staining, intracellular cytokine staining, enzyme-linked immunospot and virus-specific IFN-γ ELISA assays, and their clinical applications to determine the individual risk for opportunistic viral infections with human cytomegalovirus, Epstein-Barr virus and polyoma BK virus are discussed. The standardization of the procedure, the choice of the antigen(s) and the criteria to define cut-off values for positive responses are needed for some of these approaches before their implementation in the clinic. Nevertheless, immune monitoring combined with virological monitoring in transplant recipients is increasingly regarded as a helpful tool to identify patients at risk of infection as well as to assess treatment efficacy. Copyright © 2015. Published by Elsevier B.V.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 09/2015; 70:109-19. DOI:10.1016/j.jcv.2015.07.299 · 3.02 Impact Factor
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    ABSTRACT: To evaluate the role of human bocavirus (hBoV) as a causative agent of respiratory disease, the importance of the viral load in respiratory disease type and severity and the pathogenicity of the different hBoV species, we studied all hBoV-positive nasopharyngeal samples collected from children who attended an emergency room for a respiratory tract infection during three winters (2009-2010, 2011-2012, and 2013-2014). Human bocavirus was detected using the respiratory virus panel fast assay and real-time PCR. Of the 1,823 nasopharyngeal samples, 104 (5.7%) were positive for hBoV; a similar prevalence was observed in all three periods studied. Among hBoV-infected children, 53.8% were between 1-2 years old, and hBoV was detected alone in 57/104 (54.8%) cases. All of the detected hBoV strains belonged to genotype 1. The median hBoV load was significantly higher in samples containing strains with both the N546H and T590S mutations compared to other samples (p<0.05). Children with a single hBoV-1 infection more frequently had upper respiratory tract infections (URTIs) than those who were co-infected (37.0% vs 17.8%, respectively, p = 0.04). The duration of hospitalization was longer among children with high viral loads than that observed among children with low viral loads (8.0 ±2.2 days vs 5.0 ±1.5 days, respectively, p = 0.03), and the use of aerosol therapy was more frequent among children with high viral loads than among those with low viral loads (77.1% vs 55.7%, respectively, p = 0.04). This study shows that hBoV is a relatively uncommon but stable infectious agent in children and that hBoV1 seems to be the only strain detected in Italy in respiratory samples. From a clinical point of view, hBoV1 seems to have in the majority of healthy children relatively low clinical relevance. Moreover, the viral load influences only the duration of hospitalization and the use of aerosol therapy without any association with the site of the respiratory disease.
    PLoS ONE 08/2015; 10(8):e0135640. DOI:10.1371/journal.pone.0135640 · 3.23 Impact Factor
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    ABSTRACT: In recent years, West Nile virus (WNV) lineage 2 has been spreading and causing disease outbreaks in humans and animals in Europe. In order to characterize viral diversity, we performed full-length genome sequencing of WNV lineage 2 from human samples collected during outbreaks in Italy and Greece in 2013 and 2014. Phylogenetic analysis showed that these WNV lineage 2 genomes belonged to a monophyletic clade derived from a single introduction in Europe of the prototype Hungarian strain. Correlation of phylogenetic data with geospatial information showed geographical clustering of WNV genome sequences both in Italy and in Greece, indicating that the virus had evolved and diverged during its dispersal in Europe, leading to the emergence of novel genotypes, as it adapted to local ecological niches. These genotypes carried divergent conserved amino acid substitutions, which might have been relevant for viral adaptation, as suggested by selection pressure analysis and in silico and experimental modeling of sequence changes. In conclusion, the results of this study provide further information on WNV lineage 2 transmission dynamics in Europe and emphasize the need of WNV surveillance activities to monitor viral evolution and diversity. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 07/2015; DOI:10.1016/j.cmi.2015.07.018 · 5.77 Impact Factor
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    ABSTRACT: Infection and sepis are major health problems in cancer patients. There is a need for the identification and validation of biomarkers to improve thier early diagnosis and treatment. Emerging evidence showed that neutrophil CD64 is a highly sensitive and specific marker for systemic infection and sepis in critically ill patiens with variuous diseases but data on patients bearing solid tumors are sill lacking. Using a dedicated flow cytometric assay we evaluated neutrophil CD64 expression in patients with advanced cancer without active infections to verify if it could be utilized as a reliable biomarker of early infections also in oncologic patients.
    The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 07/2015; 38(3). · 1.78 Impact Factor
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    ABSTRACT: Because swine influenza virus infection is seldom diagnosed in humans, its frequency might be underestimated. We report a immunocompromised hematologic patient with swine influenza A(H3N2) virus in 2014 in Italy. Local pigs were the source of this human infection.
    Emerging infectious diseases 07/2015; 21(7). DOI:10.3201/eid2107.140981 · 6.75 Impact Factor
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    ABSTRACT: HRV infections are generally self-limiting in healthy subjects, whereas in immunocompromised hosts HRV infections can lead to severe complications and persistent infections. The persistence of HRV shedding could be due to the inefficient immunological control of a single infectious episode. To investigate the clinical, virologic and immunologic characteristics of pediatric HSCT recipients with HRV-PI infection. During the period 2006-2012, eight hematopoietic stem cell transplant (HSCT) recipients presented with persistent rhinovirus infection (HRV-PI, ≥30 days). Viral load and T-CD4(+), T-CD8(+), B and NK lymphocyte counts at the onset of infection were compared with those of fourteen HSCT recipients with acute HRV infection (HRV-AI, ≤15 days). The median duration of HRV positivity in patients with HRV-PI was 61 days (range 30-174 days) and phylogenetic analysis showed the persistence of a single HRV type in all patients (100%). In HSCT recipients with HRV-PI, T-CD4(+), T-CD8(+) and NK cell counts at the onset of infection were significantly lower than those observed in recipients with HRV-AI (p<0.01), while B cell counts were similar in the two groups (p= 0.25). A decrease in HRV load was associated with a significant increase in T-CD4(+), T-CD8(+)and NK lymphocyte counts in HRV-PI patients (p<0.01). This study suggests a role for cellular immunity in HRV clearance and highlights the importance of its recovery for the control of HRV infection in HSCT recipients. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of Clinical Virology 06/2015; 67. DOI:10.1016/j.jcv.2015.03.022 · 3.02 Impact Factor
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    ABSTRACT: Given the difficulty in establishing the exact time of HCMV transmission from mother to fetus, HCMV intrauterine infection was investigated in 46 infected fetuses/newborns by correlating maternal and fetal parameters with clinical outcome according to the time interval between the onset of maternal infection and prenatal diagnosis. In detail, 17/28 (60.7%) asymptomatic and 18/18 (100%) symptomatic fetuses/newborns were infected as a consequence of a primary maternal HCMV infection acquired ≤8 weeks of gestational age, while 11/28 (39.3%) asymptomatic and 0/18 (0%) symptomatic fetuses/newborns were congenitally infected when maternal infection was acquired >8 weeks'gestation. Symptomatic fetal infections appeared to be associated with a maternal primary infection occurring at ≤ 8 weeks' gestation. Cordocentesis performed at 20 weeks' gestation should be restricted to high risk infected fetuses. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Medical Virology 06/2015; DOI:10.1002/jmv.24313 · 2.35 Impact Factor
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    ABSTRACT: Little is known about the kinetics of T-cell subsets in lung transplant recipients (LTR) and their association with the occurrence of opportunistic infections (OI). To analyze the kinetics of T-lymphocyte subsets in LTR and the association between nadir CD4 T-cell count and viral infections after transplantation. Serial measurements of peripheral blood CD4 and CD8 T-cell counts obtained during the first year post-transplantation from 83 consecutive LTR and their correlation with both viral OI and community-acquired infections post-transplantation were retrospectively analyzed. LTR with a nadir CD4 T-cell count <200 cells/μl had consistently lower CD4 and CD8 T-cell counts than LTR with a nadir CD4 T-cell count >200 cells/μl (p<0.001). In LTR with a nadir CD4 T-cell count <200 cells/μl, the cumulative incidence of viral infections detected in peripheral blood and in bronchoalveolar lavage (BAL) samples was higher than in LTR with a nadir CD4 T-cell count >200 cells/μl (p=0.0012 and p=0.0058, respectively). A nadir CD4 T-cell count <200 cells/μl within the first three months post-transplantation predicted a higher frequency of viral infectious episodes in BAL samples within the subsequent six month period (p=0.0066). Stratification of patients according to nadir CD4 T-cell count may represent a new and simple approach for early identification of patients at risk for subsequent virus infections. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2015; 69. DOI:10.1016/j.jcv.2015.06.078 · 3.02 Impact Factor
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    ABSTRACT: In order to investigate the genetic diversity and patterns of the co-circulating genotypes of respiratory syncytial virus (RSV) and their possible relationships with the severity of RSV infection, we studied all of the RSV-positive nasopharyngeal samples collected from children during five consecutive winters (2009-2010, 2010-2011, 2011-2012, 2012-2013 and 2013-2014). The RSVs were detected using the respiratory virus panel fast assay and single-tube RT-PCR, their nucleotides were sequenced, and they were tested for positive selection. Of the 165 positive samples, 131 (79.4%) carried RSV-A and 34 (20.6%) RSV-B; both groups co-circulated in all of the study periods, with RSV-A predominating in all the seasons except for winter 2010-2011, which had a predominance of RSV-B. Phylogenetic analysis of the RSV-A sequences identified genotypes NA1 and ON1, the second replacing the first during the last two years of the study period. The RSV-B belonged to genotypes BA9 and BA10. BA9 was detected in all the years of the study whereas BA only desultorily. Comparison of the subjects infected by RSV-A and RSV-B types did not reveal any significant differences, but the children infected by genotype A/NA1 more frequently had lower respiratory tract infections (p<0.0001) and required hospitalisation (p = 0.007) more often than those infected by genotype A/ON1. These findings show that RSV has complex patterns of circulation characterised by the periodical replacement of the predominant genotypes, and indicate that the circulation and pathogenic role of the different RSV strains should be investigated as each may have a different impact on the host. A knowledge of the correlations between types, genotypes and disease severity may also be important in order to be able to include the more virulent strains in future vaccines.
    PLoS ONE 06/2015; 10(6):e0129369. DOI:10.1371/journal.pone.0129369 · 3.23 Impact Factor
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    Journal of Viral Hepatitis 04/2015; 2015;22:391–398. · 3.91 Impact Factor
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    ABSTRACT: In the summer of 2013, an outbreak of West Nile virus (WNV) infection occurred in the Lombardy, a region of northern Italy to the west of districts affected by WNV in previous years. Eighteen cases of human WNV infection were diagnosed-10 cases of acute WNV neuroinvasive disease and eight of WNV fever. In the same period, WNV was detected in birds (one crow) in horses (11 cases) and from mosquitoes (six pools).
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 04/2015; 15(4):278-283. DOI:10.1089/vbz.2014.1711 · 2.30 Impact Factor
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    ABSTRACT: The identification of a putative novel type human papillomaviruses (HPV) strain related to HPV-RTRX3 in a subject with penile skin warts and glans lichen sclerosus is reported. A beta-HPV-RTRX3-like strain was detected in a immunocompetent patient with glans lichen sclerosus. HPV screening was performed by PCR in L1 gene. The MY fragment showed 99% nt identity with HPV-RTRX3 and 64.5% nt identity with HPV-37. The remaining part of the L1 gene showed similarity with HPV 80, 15, 17, and 37. Based on the presence of penile lichen sclerosus and the HPV-RTRX3-like strain found in our patient, a potential correlation was hypothesized.
    The New Microbiologica: official journal of the Italian Society for Medical Virology (SIVIM) 03/2015; 38(1):91-5. · 1.78 Impact Factor
  • Antonio Piralla · Alessia Girello · Marta Premoli · Fausto Baldanti
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    ABSTRACT: A global reemergence of human enterovirus 68 (EV-D68) associated with severe respiratory illness was occurred during the 2014. We developed and validated an EV-D68-specific real-time RT-PCR for the detection of EV-D68 in respiratory samples. The rapid diagnosis of EV-D68 may contribute to better management of EV-D68 infections. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of Clinical Microbiology 02/2015; 53(5). DOI:10.1128/JCM.03691-14 · 3.99 Impact Factor
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    ABSTRACT: To evaluate the best diagnostic technique and risk factors of the human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) infection in inflammatory bowel disease (IBD). A cohort of 40 IBD patients (17 refractory) and 40 controls underwent peripheral blood and endoscopic colonic mucosal sample harvest. Viral infection was assessed by quantitative real-time polymerase chain reaction and immunohistochemistry, and correlations with clinical and endoscopic indexes of activity, and risk factors were investigated. All refractory patients carried detectable levels of HCMV and/or EBV mucosal load as compared to 13/23 (56.5%) non-refractory and 13/40 (32.5%) controls. The median DNA value was significantly higher in refractory (HCMV 286 and EBV 5.440 copies/10(5) cells) than in non-refractory (HCMV 0 and EBV 6 copies/10(5) cells; P < 0.05 and < 0.001) IBD patients and controls (HCMV and EBV 0 copies/10(5) cells; P < 0.001 for both). Refractory patients showed DNA peak values ≥ 10(3) copies/10(5) cells in diseased mucosa in comparison to non-diseased mucosa (P < 0.0121 for HCMV and < 0.0004 for EBV), while non-refractory patients and controls invariably displayed levels below this threshold, thus allowing us to differentiate viral colitis from mucosal infection. Moreover, the mucosal load positively correlated with the values found in the peripheral blood, whilst no correlation with the number of positive cells at immunohistochemistry was found. Steroid use was identified as a significant risk factor for both HCMV (P = 0.018) and EBV (P = 0.002) colitis. Finally, a course of specific antiviral therapy with ganciclovir was successful in all refractory patients with HCMV colitis, whilst refractory patients with EBV colitis did not show any improvement despite steroid tapering and discontinuation of the other medications. Viral colitis appeared to contribute to mucosal lesions in refractory IBD, and its correct diagnosis and management require quantitative real-time polymerase chain reaction assay of mucosal specimens.
    02/2015; 21(6):1915-26. DOI:10.3748/wjg.v21.i6.1915
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    ABSTRACT: The coding sequences of five human enterovirus (HEV)-C genotype 105 strains recovered in Italy, Romania and Burundi from patients with upper and lower respiratory tract infections were analyzed and phylogenetically compared with other circulating HEV-C strains. The EV-C105 was closely related with EV-C109 and EV-C118 strains. The European strains were similar to other circulating EV-C105 strains, while the two African EV-C105 clustered in a separate bootstrap-supported (>0.90) branch of P2 and P3 region trees. Minor inconsistencies in the clustering pattern of EV-C105 in the capsid region (P1) and non-capsid region (P3) suggest that recombination may have occurred in EV-C105 group B viruses. In conclusion, phylogenetic analysis revealed the circulation of two distinct EV-C105 lineages in Europe and Africa. A different pattern of evolution could be hypothesized for the two EV-C105 lineages.
    Journal of General Virology 02/2015; 96(Pt_6). DOI:10.1099/vir.0.000088 · 3.18 Impact Factor
  • Digestive and Liver Disease 02/2015; 47:e53. DOI:10.1016/j.dld.2015.01.116 · 2.96 Impact Factor
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    ABSTRACT: Liver fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C viruses. We investigated the correlation between liver fibrosis, immune activation and microbial translocation. This cross-sectional study included patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) mono-infections, HIV/HCV co-infection, and healthy controls (20 subjects/group). Peripheral blood was analysed to determine the levels of Forkhead box 3 (Foxp3) T cells, TGF-β1, CD14 (soluble and surface isoforms), IL-17 and bacterial translocation products. These measurements were correlated to the severity of liver fibrosis, measured with the FIB-4 score and transient elastography. Foxp3T cell levels were significantly elevated in HIV mono-infected and co-infected groups (p<0.0005). FIB-4 and liver stiffness values inversely correlated with TGF-β1 (p=0.0155 and p=0.0498). Bacterial DNA differed significantly in the HIV-positive compared to the other groups: HIV/HCV co-infected subjects had significantly higher serum levels of bacterial translocation products, CD14, and IL-17 levels (p<0.001). Fibrosis stage in HIV/HCV co-infection may be influenced by immune activation due either by viral infections or to bacterial translocation. Copyright © 2014. Published by Elsevier Ltd.
    Digestive and Liver Disease 11/2014; 47(3). DOI:10.1016/j.dld.2014.11.012 · 2.96 Impact Factor

Publication Stats

5k Citations
899.02 Total Impact Points


  • 1995–2015
    • Policlinico San Matteo Pavia Fondazione IRCCS
      • s.c. Cardiologia
      Ticinum, Lombardy, Italy
  • 1989–2015
    • University of Pavia
      • • Department of Public Health, Experimental and Forensic Medicine
      • • Department of Diagnostic, Paediatric, Clinical and Surgical Science
      Ticinum, Lombardy, Italy
  • 2013
    • Soroka Medical Center
      • Pediatric Infectious Disease Unit
      Be'er Sheva`, Southern District, Israel
  • 2001–2013
    • Ospedale di San Raffaele Istituto di Ricovero e Cura a Carattere Scientifico
      Milano, Lombardy, Italy
  • 1995–2008
    • Istituto di Cura e Cura a Carattere Scientifico Basilicata
      Rionero in Vulture, Basilicate, Italy
  • 2004
    • International Centre for Genetic Engineering and Biotechnology
      • Molecular Medicine Laboratory
      Trst, Friuli Venezia Giulia, Italy
  • 1999–2004
    • University of Milan
      Milano, Lombardy, Italy
  • 2003
    • University of Zurich
      • Institute of Veterinary Biochemistry and Molecular Biology
      Zürich, Zurich, Switzerland
  • 2002
    • Max von Pettenkofer-Institut
      München, Bavaria, Germany