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Crit Care. 2019 Sep 5;23(1):303. doi: 10.1186/s13054-019-2566-7.
Host susceptibility to severe influenza A virus infection.
Clohisey S1, Baillie JK2,3.
Author information
1 Division of Genetics and Genomics, Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK. 2 Division of Genetics and Genomics, Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK. j.k.baillie@ed.ac.uk. 3 Intensive Care Unit, Royal Infirmary of Edinburgh, 54 Little France Drive, Edinburgh, EH16 5SA, UK. j.k.baillie@ed.ac.uk.
Abstract
Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult. Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. As with other infectious diseases, a substantial component of susceptibility is determined by host genetics. Several genetic susceptibility variants have now been reported with varying levels of evidence. Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts. Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.
KEYWORDS:
ARDS; Genetics; Influenza; Susceptibility
PMID: 31488196 DOI: 10.1186/s13054-019-2566-7
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Host susceptibility to severe influenza A virus infection.
Clohisey S1, Baillie JK2,3.
Author information
1 Division of Genetics and Genomics, Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK. 2 Division of Genetics and Genomics, Roslin Institute, University of Edinburgh, Easter Bush, Edinburgh, EH25 9RG, UK. j.k.baillie@ed.ac.uk. 3 Intensive Care Unit, Royal Infirmary of Edinburgh, 54 Little France Drive, Edinburgh, EH16 5SA, UK. j.k.baillie@ed.ac.uk.
Abstract
Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult. Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. As with other infectious diseases, a substantial component of susceptibility is determined by host genetics. Several genetic susceptibility variants have now been reported with varying levels of evidence. Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts. Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.
KEYWORDS:
ARDS; Genetics; Influenza; Susceptibility
PMID: 31488196 DOI: 10.1186/s13054-019-2566-7
Free full text