High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier
Authors: Hulme, Katina D.; Yan, Limin; Marshall, Rebecca J.; Bloxham, Conor J.; Upton, Kyle R.; Hasnain, Sumaira Z.; Bielefeldt-Ohmann, Helle; Loh, Zhixuan; Ronacher, Katharina; Chew, Keng Yih; Gallo, Linda A.; Short, Kirsty R.
Diabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vivo murine model of type II diabetes. In vitro we show that high glucose conditions prior to IAV infection increased virus-induced barrier damage. This was associated with an increased pro-inflammatory response in endothelial cells and the subsequent damage of the epithelial junctional complex. These results were subsequently validated in vivo. This study provides the first evidence that hyperglycaemia may increase influenza severity by damaging the pulmonary epithelial-endothelial barrier and increasing pulmonary oedema. These data suggest that maintaining long-term glucose control in individuals with diabetes is paramount in reducing the morbidity and mortality associated with influenza virus infections.
Phylogenetic characterization of a reassortant H5N2 influenza A virus from a resident Mexican duck (Anas diazi)
INFECTION GENETICS AND EVOLUTION
Authors: Gaytan-Cruz, Liliana; Mateus-Anzola, Jessica; Montoya-Carrillo, Cecilia; Zarza, Heliot; Garcia-Espinosa, Gary; Ojeda-Flores, Rafael
Congregation of different migratory and resident bird species on aquatic ecosystems during winter migration increases contact rates and enhances influenza A virus (IAV) transmission. However, scarce research has been focused on the resident bird's contribution to the viral ecology at a local scale. The Mexican duck (Anas diazi) is an endemic endangered anatid from Mexico. This resident species shares aquatic habitats with migratory birds in the wetlands of Central Mexico. Therefore, here we describe the phylogenetic analysis of an IAV (A/Mexican duck/EstadodeMexico; Lerma/UIFMVZ377/2016(H5N2)) isolated in this species, during spatiotemporal concurrence with migratory anatids in the winter season. All eight gene sequences were obtained by nextgeneration sequencing. Maximum Likelihood trees were constructed using MEGA-X, with General Time Reversible + Invariant (GTR+I), Subtree Pruning and Regrafting (SPR) heuristic method, and 1000 bootstrap replicates. Similarities with six different IAV subtypes were observed through a BLAST search: H6N5, H7N7, H5N2, H4N6, H9N2, and H11N9, detected in wild ducks during 2015 in the Pacific, Central and Mississippi flyways stop sites across the United States of America and Canada. The molecular identification of this reassortant H5N2 IAV highlights the importance of resident species as a reservoir host and its potential participation in the maintenance and transmission of IAV in wetlands surrounded by rural areas.