Macrophages (Mφ) are crucial for
pathogen detection and
elimination, and also serve as a microenvironment for replication of multiple infectious pathogens. This delicate balance between
viral replication and antiviral response remains largely unknown at the
molecular level. Addressing this issue is physiologically important given the persistent
threat posed by emerging viral pathogens. Here, we demonstrate that GAS7 expression within macrophages restricts the replication of viral pathogens belonging to all major viral groups. We show that the antiviral activity of GAS7 exists even under conditions where the classical antiviral response mediated by type I
interferon is neutralized. In particular, we show that in human
monocyte-derived macrophages, silencing of GAS7 boosts the replication of multiple viral pathogens representing most relevant viral groups. These include the retroviruses HIV-1 (
human immunodeficiency virus type 1) and HIV-2 (
human immunodeficiency virus type 2), the
RNA viruses
Zika virus (positive-sense single-stranded
RNA),
Sindbis virus (single-stranded positive-sense
RNA),
Sendai virus (negative-sense single-stranded RNA), VSV
virus (negative-sense single-stranded RNA), and
measles virus (negative-sense single-stranded RNA), and the
DNA virus HSV-1 virus (double-stranded
DNA). Importantly, the antiviral activity of GAS7 is present even under conditions where type I
interferon is neutralized by the addition of the B18R
protein (which efficiently blocks the
type I receptor). Furthermore, the inventors demonstrate that by forcing macrophages to overexpress GAS7, they are further protected from HIV-1 infection compared to cells expressing this factor at normal levels. Therefore, the present invention relates to the modulation of GAS7 expression and / or activity for modulating
viral replication in macrophage populations.