FIG. 2.
Driving forces for directional spreading of viruses (adapted from reference 113 with permission of the publisher). (A) Affinity-based model for directional spreading. Downregulation of the viral receptor in the infected cells allows the establishment of a general affinity gradient between the infected and uninfected cell. Additional virus interactions with the infected cell can retain completely budded viral particles at the surface of the infected cell. Low-affinity retention on the surface of producer cells allows for diffusive movement along the cell surface (111). This process can position viruses for subsequent high-affinity interactions with target cells expressing receptor, thereby driving directional spreading of surface associated viruses. (B) Viral transmission driven by retrograde F-actin flow of the target cell. High-affinity interactions with receptor (green) in the target cell allows surface-associated viruses to engage the underlying F-actin flow (blue) to move toward the cell body of the target cell (17, 68, 69, 110, 115). This process, originally designated “virus surfing,” can promote a driving force for cell-to-cell spreading for the surface-retained viruses presented in panel A. In addition, long-term Env-receptor interactions between infected and uninfected cells can anchor target cell membranes directly at the infected cells (112). Because virus assembly can be redirected toward these sites of cell-cell contact (56), viruses can immediately engage target cell F-actin flow (blue) to move toward the target cell upon completion of assembly. (C) Viral transmission driven by actin assembly in the infected cell. In contrast to the depictions in panel B, viruses can induce actin comet tail formation (red) inside the infected cell to propel themselves toward neighboring cells (23, 30, 62). While vaccinia virus induces actin tails (red) beneath the plasma membrane of completely released viruses, capsids of the African swine fever virus induce actin tails (red) while still topologically within the cytoplasm. Such actin-propelled motion may be sufficient to drive transmission, but a combination of actin-driven movements both away from the infected cell (red) as well as toward the target cell (blue) are also plausible (81).