Figure 4.

Schematic representation of the environmental restriction concept. Human cells bear cell-intrinsic mechanisms to limit virus spread, such as intrinsic immunity by restriction factors and cell-autonomous immunity by recognition of viral components by pattern-recognition receptors (PRRs). Both pathways can lead to the induction of antiviral effectors such as interferons and cytokines, which can impair virus replication in both the infected and bystander cells. In addition, we propose that the tissue environment can provide tissue-intrinsic immunity by exerting environmental restrictions on virus replication. Such activities could be exerted via direct effects on virus particles, but we also hypothesize that tissue interactions impact the expression and activity of cell-autonomous immune mechanisms.