Pattern of activation of human antigen presenting cells by genotype GII.4 norovirus virus-like particles
- PDF / 316,182 Bytes
- 7 Pages / 595.28 x 793.7 pts Page_size
- 11 Downloads / 181 Views
RESEARCH
Open Access
Pattern of activation of human antigen presenting cells by genotype GII.4 norovirus virus-like particles Eleonora Ponterio1†, Annacarmen Petrizzo2†, Ilaria Di Bartolo1, Franco Maria Buonaguro2, Luigi Buonaguro2 and Franco Maria Ruggeri1*
Abstract Background: Virus-like particles (VLPs) from an Italian GII.4 norovirus strain were used to investigate activation and maturation of circulating antigen presenting cells (APCs) of human origin. Methods: Peripheral blood mononuclear cells (PBMCs) isolated from five healthy subjects were pulsed ex vivo with VLPs, and stained with a set of monoclonal antibodies (MAbs) for phenotypic analysis by flow cytometry. Cytokine release in cell supernatants was investigated by ELISA. Results: Norovirus VLPs induced activation and maturation of circulating APCs derived from the five donors, as well as production of IL-6, IFN-γ and TNF-α cytokines. Conclusions: The present results suggest that VLPs can activate antigen presenting cells for an efficient induction of the adaptive immune response. Keywords: Norovirus, Immunology, PBMCs, VLPs
Background Norovirus is the most important agent of gastroenteritis outbreaks worldwide, representing a relevant problem of public health [1,2]. In Europe, a recent report of the EFSA authority recognized the increasing role of norovirus in causing gastroenteritis outbreaks including foodborne [3]. Norovirus (NoV) has a single stranded RNA genome, organized in three ORFs, coding for non-structural proteins (ORF1), the major capsid protein (ORF2), and for a protein (ORF3) of still unknown function. Based on nucleotide sequences, NoVs have been classified into five genogroups (GI - GV), two of which (GI and GII) include at least 25 distinct genotypes and the majority of strains responsible for human infections [4]. Genotype GII.4 is the one most frequently associated with gastroenteritis outbreaks worldwide [5]. This genotype recurrently undergoes genetic changes, generating new variants [4]. * Correspondence: [email protected] † Equal contributors 1 Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, V.le Regina Elena, 299, 00161, Rome, Italy Full list of author information is available at the end of the article
Norovirus infection occurs at all ages, suggesting that a long-lasting protective immune response is not elicited, possibly related to a mostly strain-specific antibody response [4]. However, mechanisms of immunity toward norovirus are poorly understood, and data available on cross-protection following natural infection are contradictory [4,5]. Due to the absence of cell culture systems, most information on NoV has been obtained through the expression of the viral capsid protein in eukaryotic systems, particularly baculovirus. In insect cells, baculovirus recombinant capsid proteins self-assemble into viruslike particles (VLP) [4,5], thus providing suitable particulate antigen for diagnostic assays, for viral antigen characterization and for investigating norovirus-induced immune res
Data Loading...
