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Review
. 2020 Jun;139(6-7):941-948.
doi: 10.1007/s00439-019-02108-3. Epub 2020 Feb 5.

Human genetics of life-threatening influenza pneumonitis

Qian Zhang  1
Affiliations
Review

Human genetics of life-threatening influenza pneumonitis

Qian Zhang. Hum Genet. 2020 Jun.

Abstract

Influenza viruses infect millions of people around the globe annually, usually causing self-limited upper respiratory tract infections. However, a small but non-negligible proportion of patients suffer from life-threatening pulmonary disease. Those affected include otherwise healthy individuals, and children with primary infections in particular. Much effort has been devoted to virological studies of influenza and vaccine development. By contrast, the enormous interindividual variability in susceptibility to influenza has received very little attention. One interesting hypothesis is that interindividual variability is driven largely by the genetic makeup of the infected patients. Unbiased genomic approaches have been used to search for genetic lesions in children with life-threatening pulmonary influenza. Four monogenic causes of severe influenza pneumonitis-deficiencies of GATA2, IRF7, IRF9, and TLR3-have provided evidence that severe influenza pneumonitis can be genetic and often in patients with no other severe infections. These deficiencies highlight the importance of human type I and III IFN-mediated immunity for host defense against influenza. Clinical penetrance is incomplete, and the underlying mechanisms are not yet understood. However, human genetic studies have clearly revealed that seemingly sporadic and isolated life-threatening influenza pneumonitis in otherwise healthy individuals can be genetic.

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Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Genetic defects in the type I and III IFN pathways. Genetic defects are labeled with gene/protein names and associated diseases are labeled with color codes. Genetic defects that are not identified so far (RIG-I) or mainly lead to diseases in other pathways (JAK1, TYK2, and STAT3) are labeled in black. HSE herpes simplex encephalitis, LAV live attenuated vaccine, FLU influenza, IBD inflammatory bowel disease
See this image and copyright information in PMC

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