![ICIS_picture_Jacobsen_Nat_Comms Photo of Article Co-Authors Viejo-Borbolla, Jacobson, and Plückebaum](https://i0.wp.com/signals.cytokinesociety.org/wp-content/uploads/sites/6/2024/07/ICIS_picture_Jacobsen_Nat_Comms.jpeg?resize=678%2C381&ssl=1)
Viral modulation of type II interferon increases T cell adhesion and virus spread
Herpes and poxviruses express viroceptors, viral proteins that bind cytokines and modulate their activity. Until now, all known viroceptors that bind interferon (IFN) have been discovered exclusively in poxviruses and inhibit IFN activity through blocking the cytokine-receptor interaction. In Jacobsen et al., we report the discovery of the first IFN-binding protein in herpesviruses: glycoprotein C (gC), expressed by varicella zoster virus (VZV), binds IFN-γ with high affinity. Interestingly, VZV gC does not inhibit IFN-γ activity. Instead, VZV gC promotes IFN-γ-dependent expression of a subset of IFN-stimulated genes (ISGs), including chemokines and intercellular adhesion molecule 1 (ICAM1). This results in higher ICAM1 expression at the plasma membrane of human keratinocytes as well as higher T cell adhesion through interaction with lymphocyte function-associated antigen 1. Finally, the presence of gC during infection of keratinocytes facilitates VZV spread to peripheral blood mononuclear cells. This function is critical for VZV as this virus must spread from epithelial cells to leukocytes, T cells in particular, to disseminate systemically during primary and secondary viremia, ultimately colonizing the skin and peripheral neurons, where it establishes latency. Moreover, VZV gC activity is reminiscent of IFN-γ biased agonists that induce higher expression of specific ISGs through differential interaction with the two chains of the IFN-γ receptor (Mendoza et al., 2019, Nature, doi: 10.1038/s41586-019-0988-7). Understanding how VZV gC modulates IFN-γ activity could facilitate the development of more efficient therapies based on this cytokine.
Read the article in Nature Communications (https://doi.org/10.1038/s41467-024-49657-4)
Viral modulation of type II interferon increases T cell adhesion and virus spread