Tratamiento dirigido al complejo de ensamblaje de cadenas lineales de ubiquitina para modular la respuesta del huésped y mejorar el daño pulmonar inducido por el virus de la gripe A

Translated title of the contribution: Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury

Patricia L. Brazee, Jacob I. Sznajder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as “cytokine storm”, occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.

Translated title of the contributionTargeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury
Original languageSpanish
Pages (from-to)586-591
Number of pages6
JournalArchivos de Bronconeumologia
Volume56
Issue number9
DOIs
StatePublished - Sep 2020

Keywords

  • Acute lung injury
  • Inflammation
  • Influenza virus

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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