Viral trafficking violations in axons: The herpesvirus case

Macromolecular diffusion is essential to cell function but largely restricted by the viscosity of the cytosol and the dense meshwork of cytoskeletal filaments. The actin and microtubule cytoskeleton together with associated motors are responsible for macromolecular transport in the cytoplasm, but we still lack major insights into the nature and regulation of cargo binding to motors. Research on virus nanoparticles has provided cues to the regulation of cytoplasmic transport. To commandeer its host, a virus must elude host restrictions at multiple levels, including entry, cytoplasmic transport, replication, innate and adaptive immune recognition, and egress from the infected cell. Viruses that replicate their genomes in the nucleus use microtubule motors for trafficking toward the nuclear membrane during entry and the periphery during egress after replication. How viruses achieve different transport directionalities in the same cell has been a longstanding puzzle to cell biologists and virologists.

In their work, published in this issue of PNAS, Luxton et al. (1) use an α-herpesvirus, pseudorabies virus (PRV), to provide evidence that the composition of intracellular viruses is associated with the directional flow of the particles in axons of dorsal root ganglia neurons. PRV is a neurotropic herpesvirus whose natural hosts are pigs, and the virus is related to human herpes simplex virus (HSV). It has an icosahedral capsid, a surrounding tegument of many different proteins, and a limiting lipid envelope with glycoproteins. Like HSV, PRV infects mucosal epithelia and enters nerve termini, from where it traffics to and delivers its genome into the nucleus of the cell body. In the nucleus, the genome may give rise to infectious progeny or become latent with little gene expression. The silenced genome can be reactivated upon stress and establish a productive infection in the peripheral nervous system and, later, also in the mucosal periphery, where newly …