Journal
SCIENCE
Volume 374, Issue 6571, Pages 1080-1086Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abj7965
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Funding
- Howard Hughes Medical Institute
- Rockefeller University
- St. Giles Foundation
- National Institutes of Health (NIH) [R01AI088364]
- National Center for Advancing Translational Sciences (NCATS)
- NIH Clinical and Translational Science Award (CTSA) program [UL1 TR001866]
- Emergent Ventures
- Mercatus Center at George Mason University
- Yale Center for Mendelian Genomics
- National Human Genome Research Institute (NHGRI) [UM1HG006504, U24HG008956]
- Yale High Performance Computing Center [S10OD018521]
- Fisher Center for Alzheimer's Research Foundation
- Meyer Foundation
- French National Research Agency (ANR) under the Investments for the Future program [ANR-10-IAHU-01]
- Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence [ANR-10-LABX-62-IBEID]
- French Foundation for Medical Research (FRM) [EQU201903007798]
- FRM
- ANR GENCOVID project
- ANRS-COV05 project
- ANR AABIFNCOV project [ANR-20-CO11-0001]
- Square Foundation
- Grandir-Fonds de solidarite pour l'enfance
- SCOR Corporate Foundation for Science
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- REACTing-INSERM
- University of Paris
- ANR GENVIR project [ANR-20-CE93-003]
- Agence Nationale de la Recherche (ANR) [ANR-20-CO11-0001] Funding Source: Agence Nationale de la Recherche (ANR)
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Disease and inflammation are rare outcomes of viral infection in humans, often due to a failure in cell-intrinsic and leukocytic immunity to viruses. Inflammation indicates the efforts of newly recruited and activated leukocytes to resolve infection. Genetic studies can help clarify the underlying causes of inflammation and disease in viral infections.
Disease and accompanying inflammation are uncommon outcomes of viral infection in humans. Clinical inflammation occurs if steady-state cell-intrinsic and leukocytic immunity to viruses fails. Inflammation attests to the attempts of newly recruited and activated leukocytes to resolve infection in the blood or tissues. In the confusing battle between a myriad of viruses and cells, studies of human genetics can separate the root cause of inflammation and disease from its consequences. Single-gene inborn errors of cell-intrinsic or leukocytic immunity underlying diverse infections in the skin, brain, or lungs can help to clarify the human determinants of viral disease. The genetic elucidation of immunological deficits in a single patient with a specific vulnerability profile can reveal mechanisms of inflammation and disease that may be triggered by other causes, inherited or otherwise, in other patients. This human genetic dissection of viral infections is giving rise to a new biology and a new medicine.
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