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J Interferon Cytokine Res . Differential Leukocyte Expression of IFITM1 and IFITM3 in Patients with Severe Pandemic Influenza A(H1N1) and COVID-19

tetano

Editor, Senior Moderator
J Interferon Cytokine Res


. 2022 Jun 14.
doi: 10.1089/jir.2022.0036. Online ahead of print.
Differential Leukocyte Expression of IFITM1 and IFITM3 in Patients with Severe Pandemic Influenza A(H1N1) and COVID-19


Nora E Regino-Zamarripa[SUP] 1 2 3 [/SUP], Gustavo Ramírez-Martínez[SUP] 1 [/SUP], Luis Armando Jiménez-Álvarez[SUP] 1 [/SUP], Alfredo Cruz-Lagunas[SUP] 1 [/SUP], Itzel Alejandra Gómez-García[SUP] 1 3 [/SUP], Sergio Ignacio-Cortés[SUP] 1 3 [/SUP], José Eduardo Márquez-García[SUP] 1 [/SUP], Lynette Miroslava Pacheco-Hernández[SUP] 1 3 [/SUP], Jazmín Ariadna Ramírez-Noyola[SUP] 1 4 [/SUP], Rodrigo Barquera[SUP] 5 [/SUP], Criselda Mendoza-Milla[SUP] 1 3 [/SUP], Cesar Luna-Rivero[SUP] 6 [/SUP], José Guillermo Domínguez-Cherit[SUP] 3 7 [/SUP], Remedios Ramírez-Rangel[SUP] 8 [/SUP], Tatiana Sofía Rodríguez-Reyna[SUP] 9 [/SUP], Carmen M Hernández-Cárdenas[SUP] 10 [/SUP], José Alberto Choreño-Parra[SUP] 1 3 [/SUP], Gloria León-Ávila[SUP] 11 [/SUP], Joaquín Zúñiga[SUP] 1 3 [/SUP]



Affiliations

Abstract

Interferon-induced transmembrane (IFITM) proteins mediate protection against enveloped viruses by blocking membrane fusion at endosomes. IFITM1 and IFITM3 are crucial for protection against influenza, and various single nucleotide polymorphisms altering their function have been linked to disease susceptibility. However, bulk IFITM1 and IFITM3 mRNA expression dynamics and their correlation with clinical outcomes have not been extensively addressed in patients with respiratory infections. In this study, we evaluated the expression of IFITM1 and IFITM3 in peripheral leukocytes from healthy controls and individuals with severe pandemic influenza A(H1N1) or coronavirus disease 2019 (COVID-19). Comparisons between participants grouped according to their clinical characteristics, underlying disease, and outcomes showed that the downregulation of IFITM1 was a distinctive characteristic of severe pandemic influenza A(H1N1) that correlated with outcomes, including mortality. Conversely, increased IFITM3 expression was a common feature of severe pandemic influenza A(H1N1) and COVID-19. Using a high-dose murine model of infection, we confirmed not only the downregulation of IFITM1 but also of IFITM3 in the lungs of mice with severe influenza, as opposed to humans. Analyses in the comparative cohort also indicate the possible participation of IFITM3 in COVID-19. Our results add to the evidence supporting a protective function of IFITM proteins against viral respiratory infections in humans.

Keywords: IFITM1; IFITM3; influenza A(H1N1); pandemic influenza; pneumonia.
 
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