Argentinian potato leafroll virus P0 protein: Novel activities for a previously known suppressor
PLANT PATHOLOGY
Authors: Barrios Baron, Maria P.; Delfosse, Veronica C.; Agrofoglio, Yamila C.; Nahirnak, Vanesa; Almasia, Natalia I.; Vazquez Rovere, Cecilia; Distefano, Ana J.
Abstract
The potato leafroll virus (PLRV) P0 protein (P0(PL)) is a suppressor of RNA silencing. In this study, we showed that P0 protein from an Argentinian isolate of PLRV (P0(PL-Ar)) has an additional activity not described for other PLRV or P0 proteins from poleroviruses. Besides reporting that P0(PL-Ar) displays both local and systemic silencing suppressor activity, we demonstrated, for the first time, that P0(PL-Ar) impedes accumulation of dsRNA-derived siRNAs. We also showed that P0(PL-Ar) interacts with Solanum tuberosum SKP1 orthologue (StSKP1) and triggers destabilization of ARGONAUTE 1 (AGO1) and that these actions are mediated by the F-box-like domain. A mutant in the GW/WG motif within the P0(PL-Ar) F-box-like motif lost the suppression activity, the interaction with StSKP1 and abolished AGO1 decay. Interestingly, a mutant in the L76/P77 residues within the P0(PL-Ar) F-box-like motif, which lost the suppression activity and the interaction with StSKP1, retained the capacity to enable AGO1 decay. Thus, unlike other P0 proteins of previously characterized poleroviruses, P0(PL-Ar) seems to have a dual activity, according to the findings of this study. This protein would act at both an upstream and a downstream step of the RNA silencing pathway: upstream of Dicer-like enzyme (DCL)-mediated primary siRNA production and downstream at the RNA-induced silencing complex (RISC) complex level. Our results contribute to the understanding of the different ways PLRV P0 proteins function as silencing suppressors.
Long-term omalizumab efficacy in allergic rhinitis
IMMUNOLOGY LETTERS
Authors: Cavaliere, Carlo; Begvarfaj, Elona; Incorvaia, Cristoforo; Sposato, Bruno; Brunori, Marco; Ciofalo, Andrea; Greco, Antonio; de Vincentiis, Marco; Masieri, Simonetta
Abstract
Background: Omalizumab therapy was found to be safe and effective as an add-on therapy for patients with poorly controlled severe asthma. Although several studies over the last decade have demonstrated its efficacy in other Immunoglobulin E related diseases, its use in such conditions is off-label. Objective: This study aimed to assess the effectiveness of long-term therapy with Omalizumab in patients with persistent severe allergic rhinitis and inadequately controlled severe asthma. Methods: Patients with poorly controlled severe asthma and persistent allergic rhinitis were enrolled and treated with Omalizumab for 36 months with every four-week subcutaneous administration. The efficacy assessment included the severity of AR symptoms every six months using Visual Analogue Scale, Asthma Control Test, nasal endoscopy, spimmetry, and biomarkers (blood eosinophils and neutrophils, fractional exhaled nitric oxide, total IgE). Results: Eleven patients aged between 26 and 70 years were enrolled, and 10 completed the study. A significant improvement of allergic rhinitis symptoms, Asthma Control Test, and lung function was observed. There was also a reduction in the status of the biomarkers at the end of the study. Conclusion: Long-term therapy with Omalizumab was effective and safe in treating severe persistent allergic rhinitis and concomitant asthma.