tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2020 Oct 12;202008203.
doi: 10.1073/pnas.2008203117. Online ahead of print.
Glycomic analysis of host response reveals high mannose as a key mediator of influenza severity
Daniel W Heindel[SUP] 1 [/SUP], Sujeethraj Koppolu[SUP] 1 [/SUP], Yue Zhang[SUP] 1 [/SUP], Brian Kasper[SUP] 1 [/SUP], Lawrence Meche[SUP] 1 [/SUP], Christopher A Vaiana[SUP] 1 [/SUP], Stephanie J Bissel[SUP] 2 [/SUP], Chalise E Carter[SUP] 3 [/SUP], Alyson A Kelvin[SUP] 4 [/SUP], Mohamed Elaish[SUP] 5 6 [/SUP], Joaquin Lopez-Orozco[SUP] 7 [/SUP], Bin Zhang[SUP] 8 [/SUP], Bin Zhou[SUP] 9 [/SUP], Tsui-Wen Chou[SUP] 9 [/SUP], Lauren Lashua[SUP] 9 [/SUP], Tom C Hobman[SUP] 5 [/SUP], Ted M Ross[SUP] 3 [/SUP], Elodie Ghedin[SUP] 9 10 [/SUP], Lara K Mahal[SUP] 11 [/SUP]
Affiliations
Abstract
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.
Keywords: MBL2; lectin array; lectin microarray; mannan binding lectin; mannose binding lectin.
. 2020 Oct 12;202008203.
doi: 10.1073/pnas.2008203117. Online ahead of print.
Glycomic analysis of host response reveals high mannose as a key mediator of influenza severity
Daniel W Heindel[SUP] 1 [/SUP], Sujeethraj Koppolu[SUP] 1 [/SUP], Yue Zhang[SUP] 1 [/SUP], Brian Kasper[SUP] 1 [/SUP], Lawrence Meche[SUP] 1 [/SUP], Christopher A Vaiana[SUP] 1 [/SUP], Stephanie J Bissel[SUP] 2 [/SUP], Chalise E Carter[SUP] 3 [/SUP], Alyson A Kelvin[SUP] 4 [/SUP], Mohamed Elaish[SUP] 5 6 [/SUP], Joaquin Lopez-Orozco[SUP] 7 [/SUP], Bin Zhang[SUP] 8 [/SUP], Bin Zhou[SUP] 9 [/SUP], Tsui-Wen Chou[SUP] 9 [/SUP], Lauren Lashua[SUP] 9 [/SUP], Tom C Hobman[SUP] 5 [/SUP], Ted M Ross[SUP] 3 [/SUP], Elodie Ghedin[SUP] 9 10 [/SUP], Lara K Mahal[SUP] 11 [/SUP]
Affiliations
- PMID: 33046650
- DOI: 10.1073/pnas.2008203117
Abstract
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.
Keywords: MBL2; lectin array; lectin microarray; mannan binding lectin; mannose binding lectin.