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- Title
Viral modulation of type II interferon increases T cell adhesion and virus spread.
- Authors
Jacobsen, Carina; Plückebaum, Nina; Ssebyatika, George; Beyer, Sarah; Mendes-Monteiro, Lucas; Wang, Jiayi; Kropp, Kai A.; González-Motos, Víctor; Steinbrück, Lars; Ritter, Birgit; Rodríguez-González, Claudio; Böning, Heike; Nikolouli, Eirini; Kinchington, Paul R.; Lachmann, Nico; Depledge, Daniel P.; Krey, Thomas; Viejo-Borbolla, Abel
- Abstract
During primary varicella zoster virus (VZV) infection, infected lymphocytes drive primary viremia, causing systemic dissemination throughout the host, including the skin. This results in cytokine expression, including interferons (IFNs), which partly limit infection. VZV also spreads from skin keratinocytes to lymphocytes prior to secondary viremia. It is not clear how VZV achieves this while evading the cytokine response. Here, we show that VZV glycoprotein C (gC) binds IFN-γ and modifies its activity, increasing the expression of a subset of IFN-stimulated genes (ISGs), including intercellular adhesion molecule 1 (ICAM1), chemokines and immunomodulatory genes. The higher ICAM1 protein level at the plasma membrane of keratinocytes facilitates lymphocyte function-associated antigen 1-dependent T cell adhesion and expression of gC during infection increases VZV spread to peripheral blood mononuclear cells. This constitutes the discovery of a strategy to modulate IFN-γ activity, upregulating a subset of ISGs, promoting enhanced lymphocyte adhesion and virus spread. Here, Jacobsen et al show that Varicella zoster virus glycoprotein C binds interferon gamma and induces biased signalling through its receptor, leading to higher expression of adhesion molecules, more T cell adhesion and viral spread from epithelial cells.
- Subjects
INTERFERON gamma; T cells; CELL adhesion; MONONUCLEAR leukocytes; INTERFERON receptors; CD54 antigen; VIRAL transmission; EPITHELIAL cells
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-49657-4