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Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

ABSTRACT: Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of pseudostratified primary human airway epithelium, we here demonstrate that infection with both IAV and SARS-CoV-2 resulted in distinct metabolic changes including increases in lactate dehydrogenase A (LDHA) expression and LDHA-mediated lactate formation. Interestingly, LDHA regulated both basal and induced mitochondrial anti-viral signaling protein (MAVS)-dependent type I interferon (IFN) responses to promote IAV, but not SARS-CoV-2, replication. Our data demonstrate that LDHA and lactate promote IAV but not SARS-CoV-2 replication by inhibiting MAVS-dependent induction of type I IFN in primary human airway epithelium.

SUBMITTER: Thyrsted J

PROVIDER: S-EPMC8555494 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

Thyrsted Jacob J Storgaard Jacob J Blay-Cadanet Julia J Heinz Alexander A Thielke Anne Laugaard AL Crotta Stefania S de Paoli Frank F Olagnier David D Wack Andreas A Hiller Karsten K Hansen Anne Louise AL Holm Christian Kanstrup CK

iScience 20211015 11

Pathogenic viruses induce metabolic changes in host cells to secure the availability of biomolecules and energy to propagate. Influenza A virus (IAV) and severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) both infect the human airway epithelium and are important human pathogens. The metabolic changes induced by these viruses in a physiologically relevant human model and how this affects innate immune responses to limit viral propagation are not well known. Using an ex vivo model of ps ...[more]

PMID: 34746710

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Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

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Influenza A induces lactate formation to inhibit type I IFN in primary human airway epithelium.

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