TY - JOUR T1 - The metabolite succinate inhibits influenza virus replication through succinylation and nuclear retention of the viral nucleoprotein JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.LSC-2022.119 VL - 8 IS - suppl 8 SP - 119 AU - Adeline Cezard AU - Antoine Guillon AU - Deborah Bréa-Diakite AU - Alan Wacquiez AU - Thomas Baranek AU - Jérôme Bourgeais AU - Frédéric Picou AU - Virginie Vasseur AU - Léa Meyer AU - Adrien Auvet AU - José M Carballido AU - Lydie Nadal Desbarats AU - Florent Dingli AU - Andrei Turtoi AU - Audrey Le Gouellec AU - Florence Fauvelle AU - Amélie Donchet AU - Thibaut Crépin AU - Pieter S. Hiemstra AU - Christophe Paget AU - Damarys Loew AU - Olivier Hérault AU - Nadia Naffakh AU - Ronan Le Goffic AU - Mustapha Si-Tahar Y1 - 2022/03/10 UR - http://openres.ersjournals.com/content/8/suppl_8/119.abstract N2 - Influenza causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during influenza infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we demonstrated that influenza virus infection induces a major reprogramming of lung metabolism. We focused on mitochondria-derived succinate that we found to accumulate both in the respiratory fluids of virus-challenged mice and of patients with influenza-related pneumonia. We found that succinate displays a potent antiviral activity in vitro as it inhibits the multiplication of influenza A/H1N1 and A/H3N2 strains and strongly decreases virus-triggered metabolic perturbations and inflammatory responses. Moreover, mice receiving succinate through the intranasal route showed reduced viral loads in lung tissues and had an increased survival rate compared to control animals. The antiviral mechanism involves a succinate-dependent post-translational modification, i.e. succinylation, of the viral nucleoprotein (NP). Succinylation of NP could alter its electrostatic interactions with viral RNA and could further impair the formation and trafficking of viral ribonucleoprotein complexes. Hence, succinate efficiently disrupts the influenza replication cycle; this opens up new avenues for improved treatment of influenza pneumonia.FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 119.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -