Magic™ Anti-IAV Monoclonal antibody, Clone N29723JGB2

In this study, we demonstrated an essential function of the hexosamine biosynthesis pathway (HBP)-associated O-linked beta-N-acetylglucosamine (O-GlcNAc) signaling in influenza A virus (IAV)-induced cytokine storm. O-GlcNAc transferase (OGT), a key enzyme for protein O-GlcNAcylation, mediated IAV-induced cytokine production. Upon investigating the mechanisms driving this event, we determined that IAV induced OGT to bind to interferon regulatory factor-5 (IRF5), leading to O-GlcNAcylation of IRF5 on serine-430.O-GlcNAcylation of IRF5 is required for K63-linked ubiquitination of IRF5 and subsequent cytokine production. Analysis of clinical samples revealed that IRF5 is O-GlcNAcylated, and higher levels of proinflammatory cytokines correlated with higher levels of blood glucose in IAV-infected patients. We identified a molecular mechanism by which HBP-mediated O-GlcNAcylation regulates IRF5 function during IAV infection, highlighting the importance of glucose metabolism in IAV-induced cytokine storm.

Influenza B virus (IBV) is one of the most important human respiratory viruses: it causes approximately one-third of the global influenza-related disease burden each year. However, compared with the several pathogenicity-related molecular markers that have been identified for influenza A virus (IAV), little is known about potential IBV pathogenicity-related markers. Here, although the IBV strain B/Anhui-Tunxi/1528/2014 (AH1528/14) exhibited a more efficient replication abilityin vitroand higher pathogenicityin vivocompared with IBV strain B/Anhui-Baohe/127/2015 (AH127/15), only three amino acids differences (HA(A390E), NA(N342D)and PB1(V212I)) were observed among their full genomes. The contributions of each amino acid difference to the virus pathogenicity were further investigated. Compared with the wild type IBV virus rAH127, the recombinant virus harbouring a single substitution of HA(A390E)had a similar phenotype, whereas the recombinant virus harbouring PB1(V212I)replicated to a moderately higher titre in both MDCK cells and in mice. Notably, the virus harbouring NA(N342D)showed significantly better growth properties in MDCK cells and higher fatality rates in mice. In addition, the presence of NA(N342D)dramatically enhanced the viral neuraminidase activity. In conclusion, our study identified a novel IBV molecular marker, NA(N342D), that could significantly increase the virulence of IBV in mice.