Biology subjects

Storgaard, J.

Publications and source records attributed to Storgaard, J..

2 recordsLinked to original sources

bioRxiv2026

Glutamate transporter xCT is important for cGAS-dependent interferon responses to DNA and to HSV-1

Metabolic reprogramming is a key component of antiviral immunity, yet how metabolite transport regulates innate immune signaling remains incompletely understood. Here, we show that infection with herpes simplex virus 1 (HSV-1) and stimulation with cytosolic DNA induce the cellular export of glutamate via the xCT (SLC7A11) transporter and that inhibition of xCT reduces cellular resistance to viral replication. Mechanistically, xCT inhibition impaired cGAS-STING signaling by reducing DNA-induced cGAMP production, thereby diminishing type I interferon (IFN/{beta}) responses and downstream induction of interferon-stimulated genes. Interestingly, modulating intracellular glutamate levels through inhibition of other glutamate pathways, e.g., glutaminolysis or glutamate import, also affected cellular IFN responses, suggesting that glutamate is a central control knob for DNA sensing. Finally, we demonstrate that HSV-1 suppresses xCT expression via a mechanism dependent on the immediate early viral protein ICP27, thereby promoting viral replication by limiting cGAS-dependent IFN induction. Together, these findings identify xCT-dependent glutamate transport as a critical metabolic regulator of cGAS-STING-mediated antiviral immunity.

immunology↗

bioRxiv2025

MAVS is Important for Antiviral Defense Against InfluenzaA Virus in a Human Respiratory Epithelium Model

The respiratory epithelium is an important immunological barrier and the first line of defense against influenza A virus. In mice and in various cellular systems, induction of type I interferons (IFN/{beta}) during IAV infections is known to depend on cytosolic RNA sensors RIG-I and MDA5 and on the adaptor molecule MAVS. Until now, it has not been possible to directly test the importance of MAVS for induction of IFNs and for resistance to IAV infection in primary human respiratory epithelium. Here, we used CRISPR-Cas9 to establish MAVS-deficient cultures of primary human respiratory epithelium using the air-liquid interphase culture system. Using this setup, we show that MAVS is indeed required for the induction of type I and type III IFNs and subsequently for the induction of IFN-stimulated genes in response to IAV infection in human primary respiratory epithelium. Finally, we demonstrate that MAVS is important for restricting viral replication in this model. In conclusion, we demonstrate that MAVS plays a non-redundant protective role during IAV infection in primary human respiratory epithelium.

immunology↗