Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane

Herpes simplex virus capsids are assembled and packaged in the nucleus and move by diffusion
through the nucleoplasm to the nuclear envelope for egress. Analyzing their motion
provides conclusions not only on capsid transport but also on the properties of the nuclear
environment during infection. We utilized live-cell imaging and single-particle tracking to
characterize capsid motion relative to the host chromatin. The data indicate that as the chromatin
was marginalized toward the nuclear envelope it presented a restrictive barrier to the
capsids. However, later in infection this barrier became more permissive and the probability
of capsids to enter the chromatin increased. Thus, although chromatin marginalization initially
restricted capsid transport to the nuclear envelope, a structural reorganization of the
chromatin counteracted that to promote capsid transport later. Analyses of capsid motion
revealed that it was subdiffusive, and that the diffusion coefficients were lower in the chromatin
than in regions lacking chromatin. In addition, the diffusion coefficient in both regions
increased during infection. Throughout the infection, the capsids were never enriched at the
nuclear envelope, which suggests that instead of nuclear export the transport through the
chromatin is the rate-limiting step for the nuclear egress of capsids. This provides motivation
for further studies by validating the importance of intranuclear transport to the life cycle of
HSV-1.