2020/10/12 by Daniel W. Heindel, Sujeethraj Koppolu, Yue Zhang +16 · 1 voice
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · Medicine · #Glycosylation and Glycoproteins Research #Immune Cell Function and Interaction #Influenza Virus Research Studies
paper · doi:10.1073/pnas.2008203117
openalex publication_date 2020/10/12 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Influenza virus infections cause a wide variety of outcomes, from mild disease to 3 to 5 million cases of severe illness and ∼290,000 to 645,000 deaths annually worldwide. The molecular mechanisms underlying these disparate outcomes are currently unknown. Glycosylation within the human host plays a critical role in influenza virus biology. However, the impact these modifications have on the severity of influenza disease has not been examined. Herein, we profile the glycomic host responses to influenza virus infection as a function of disease severity using a ferret model and our lectin microarray technology. We identify the glycan epitope high mannose as a marker of influenza virus-induced pathogenesis and severity of disease outcome. Induction of high mannose is dependent upon the unfolded protein response (UPR) pathway, a pathway previously shown to associate with lung damage and severity of influenza virus infection. Also, the mannan-binding lectin (MBL2), an innate immune lectin that negatively impacts influenza outcomes, recognizes influenza virus-infected cells in a high mannose-dependent manner. Together, our data argue that the high mannose motif is an infection-associated molecular pattern on host cells that may guide immune responses leading to the concomitant damage associated with severity.