EP4683715A1 — Modulating the expression and/or activity of gas7 for modulating viral replication

USPTO Abstract

Macrophages (MØ) are critical for the detection and clearance of pathogens and yet also serve as replication niches for multiple infectious agents. This delicate balance between viral replication and antiviral response remains poorly understood at the molecular level. Addressing this question is of physiological importance given the ever-present threat posed by emerging viral pathogens. Now, the inventors show that the expression of GAS7 in macrophages limits the replication of viral pathogens belonging to all the major viral groups. They show that the antiviral activity of GAS7 is present even in conditions where the classical antiviral response mediated by type I Interferon is neutralized. In particular, the inventor shows that in human monocyte-derived macrophages, silencing GAS7 boosts the replication of multiple viral pathogens representative of the most relevant viral groups. These include the retroviruses HIV- 1 and HIV-2, the RNA viruses ZIKA (RNAss +), SINDBIS (RNAss +), Sendai (RNAss-), VSV (RNAss-) and Measles (RNAss-), and the DNA virus HSV-1 (DNA ds). Importantly, the antiviral activity of GAS7 is present even in conditions where type I Interferon is neutralized, by the addition of the B18R protein (which blocks efficiently type I receptor). Moreover, the inventors show that enforcing the over-expression of GAS7 by macrophages further protects them against HIV-1 infection, compared with cells expressing normal levels of this factor. Accordingly, the present invention relates to the modulation of the expression and/or activity of GAS7 for modulating viral replication in a population of macrophages.