Transmembrane domain of IFITM3 is responsible for its interaction with influenza virus HA_(2) subunit

Interferon-inducible transmembrane protein 3(IFITM3)inhibits influenza virus infection by blocking viral membrane fusion,but the exact mechanism remains elusive.Here,we investigated the function and key region of IFITM3 in blocking influenza virus entry mediated by hemagglutinin(HA).The restriction of IFITM3 on HAmediated viral entry was confirmed by pseudovirus harboring HA protein from H5 and H7 influenza viruses.Subcellular co-localization and immunocoprecipitation analyses revealed that IFITM3 partially co-located with the full-length HA protein and could directly interact with HA_(2) subunit but not HA_(1) subunit of H5 and H7 virus.Truncated analyses showed that the transmembrane domain of the IFITM3 and HA_(2) subunit might play an important role in their interaction.Finally,this interaction of IFITM3 was also verified with HA_(2) subunits from other subtypes of influenza A virus and influenza B virus.Overall,our data demonstrate for the first time a direct interaction between IFITM3 and influenza HA protein via the transmembrane domain,providing a new perspective for further exploring the biological significance of IFITM3 restriction on influenza virus infection or HA-mediated antagonism or escape.

A linear relationship between De Ritis ratio and mortality in hospitalized patients with COVID-19:A secondary analysis based on a large retrospective cohort study

Background and aims:Although some studies have identified a possible link between the De Ritis ratio and the mortality of patients with COVID-19),the predictive value and the optimal cut-value remain unclear.This study aimed to explore the correlation between the De Ritis ratio and mortality in hospitalized COVID-19.Methods:The data for this cohort study came from a retrospective cohort study that was carried out in a medical system in New York City.The primary outcome was the in-hospital mortality of included patients.The researchers ran multivariate Cox regression analyses,curve fitting,and subgroup analysis to support our findings.Overall survival in different De Ritis ratio groups was plotted as Kaplan-Meier survival curves.Results:The study enrolled 4371 participants with COVID-19 from March 1,2020 to April 16,2020.The overall mortality was 24.8%(1082/4371).The curve fitting analyses indicated that the De Ritis ratio has a positive linear connection with mortality in patients with COVID-19.After adjusting for all covariates,participants with a De Ritis ratio≥2 exhibited 1.29 times the risk of in-hospital mortality compared with those with a De Ritis ratio<1(hazard ratio 1.29,95%confidence interval 1.02-1.62,p=0.031).The p for trend was<0.05 for all models.Patients in the group with a De Ritis ratio≥2 experienced the shortest survival time in the Kaplan-Meier survival analysis.Conclusions:A higher baseline De Ritis ratio is correlated with a corresponding higher mortality among hospitalized people with COVID-19.