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  • Article: Molecular epidemiology and genetic diversity of human rhinovirus affecting hospitalized children in Rome.
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    ABSTRACT: Human rhinoviruses (HRV) have been re-classified into three species (A-C), but the recently discovered HRV-C strains are not fully characterized yet. This study aimed to undertake a molecular and epidemiological characterization of HRV strains infecting children hospitalized over one year in two large research hospitals in Rome. Nasal washings from single HRV infections were retrospectively subjected to phylogenetic analysis on two genomic regions: the central part of the 5'Untranslated Region (5'UTR) and the Viral Protein (VP) 4 gene with the 5' portion of the VP2 gene (VP4/2). Forty-five different strains were identified in 73 HRV-positive children: 55 % of the cases were HRV-A, 38 % HRV-C and only 7 % HRV-B. HRV-C cases were less frequent than HRV-A during summer months and more frequent in cases presenting wheezing with respect to HRV-A. Species distribution was similar with respect to patient age, and seasonality differed during summer months with fewer HRV-C than HRV-A cases. On admission, a significantly higher number of HRV-C cases presented with wheezing with respect to HRV-A. The inter- and intra-genotype variability in VP4/2 was higher than in 5'UTR; in particular, HRV-A patient VP4/2 sequences were highly divergent (8-14 %) at the nucleotide level from those of their reference strains, but VP4 amino acid sequence was highly conserved. In HRV-C isolates, the region preceding the initiator AUG, the amino acids involved in VP4 myristoylation, the VP4-VP2 cleavage site and the cis-acting replication element were highly conserved. Differently, VP4 amino acid conservation was significantly lower in HRV-C than in HRV-A strains, especially in the transiently exposed VP4 N-terminus. This study confirmed the high number of different HRV genotypes infecting hospitalized children over one year and reveals a greater than expected variability in HRV-C VP4 protein, potentially suggestive of differences in replication.
    Medical Microbiology and Immunology 04/2013; · 3.83 Impact Factor
  • Article: Antiviral activity of the interferon α family: biological and pharmacological aspects of the treatment of chronic hepatitis C.
    Carolina Scagnolari, Guido Antonelli
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    ABSTRACT: Introduction: Type I interferons (IFNs) comprise a group of at least 13 structurally related subtypes of IFN-α with similar, but not identical, biological activities. Each subtype displays a unique activity profile; only IFN-α2a and IFN-α2b subtypes together with natural IFN-α preparations are currently used in the clinical practice, so that the remaining IFN-α subtypes are a still unexploited reservoir of opportunity also in the new era of direct-acting antiviral agents for the treatment of hepatitis C virus (HCV). Areas covered: This paper reviews recent progress in the study of the biology of IFN family, the antiviral action mechanism and the strategies employed by HCV to evade IFN action. Currently available IFN preparations for the treatment of chronic hepatitis C infection are described and what is currently known on the pharmacokinetics, pharmacodynamics and immunogenicity of IFN-α preparations used in clinical practice are summarized. Expert opinion: The characterization of multifunctional nature of IFN system together with recent advances in the identification of HCV IFN evasion strategies and the variety of host factors influencing IFN treatment response should be considered to improve HCV and other infectious diseases treatment in the future.
    Expert opinion on biological therapy 01/2013; · 3.22 Impact Factor
  • Article: USUTU VIRUS GROWTH IN HUMAN CELL LINES: INDUCTION OF AND SENSITIVITY TO TYPE I AND III INTERFERONS.
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    ABSTRACT: The mechanisms of Usutu virus (USUV) pathogenesis are largely unknown. The aim of this study was to evaluate the sensitivity of USUV to interferon (IFN) and the capacity of USUV to stimulate IFN production. Initial experiments were conducted to characterize the susceptibility of human cell lines to USUV infection and to evaluate the single-growth cycle replication curve of USUV. Results indicate that USUV is able to infect a variety of human cell lines, completing the replication cycle in Hep-2 and Vero cells within 48 hours. Pretreatment of cells with type I and III IFNs significantly inhibited the replication of USUV. However, the inhibitory effects of IFNs were considerably less if IFN was added after viral infection had been initiated. Also, USUV weakly induced type I and III IFNs.
    Journal of General Virology 12/2012; · 3.36 Impact Factor
  • Article: High detection rate of human papillomavirus in anal brushings from women attending a proctology clinic.
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    ABSTRACT: To study human papillomavirus (HPV) anal infection in anal brushings from women attending a proctology clinic, and compare results with those obtained from paired cervical brushings. Women attending a university hospital proctology clinic for anal conditions or as part of a screening campaign, were enrolled consecutively, excluding those reporting previous HPV-related pathologies. HPV genotypes in anal and cervical brushings were determined by sequencing and, in most cases, type-specific viral loads were measured. HPV DNA was detected in 28.3% of anal brushings, with 47.4% of HPV genotypes being high risk. Cervical HPV detection was at almost the same rate but HPV status was discordant in about half those women with at least one positive specimen. Abnormal cytological findings were more common in anal than in cervical samples, in particular in the proctology outpatients. Viral load measurements excluded the existence of a multiple infection with genotypes detected in discordant anal- and cervical-paired samples and showed a significant correlation between anal and cervical paired concordant samples. The high rate of HPV detection in anal brushings that is not usually related to HPV positivity in cervical brushings could provide support for offering HPV DNA tests to women attending proctology clinics.
    The Journal of infection 05/2012; 65(3):255-61. · 4.13 Impact Factor
  • Article: Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus.
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    ABSTRACT: The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.
    Medical Microbiology and Immunology 03/2012; 201(3):311-7. · 3.83 Impact Factor

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