The Herpes Simplex Virus pUL16 and pUL21 Proteins Prevent Capsids from Docking at Nuclear Pore Complexes

After entry into cells, herpes simplex virus (HSV) nucleocapsids dock at nuclear pore complexes (NPCs) through which viral genomes are released into the nucleoplasm where viral gene expression, genome replication, and early steps in virion assembly take place. After their assembly, nucleocapsids are translocated to the cytoplasm for final virion maturation. Nascent cytoplasmic nucleocapsids are prevented from binding to NPCs and delivering their genomes to the nucleus from which they emerged, but how this is accomplished is not understood. Here we report that HSV pUL16 and pUL21 deletion mutants accumulate empty capsids at the cytoplasmic face of NPCs late in infection. Additionally, prior expression of pUL16 and pUL21 prevented incoming nucleocapsids from docking at NPCs, delivering their genomes to the nucleus and initiating viral gene expression. Both pUL16 and pUL21 localized to the nuclear envelope, placing them in an appropriate location to interfere with nucleocapsid/NPC interactions. Despite the very high prevalence of HSV infections worldwide and many decades of research focused on these important human pathogens, questions related to fundamental aspects of HSV biology remain unanswered. We have provided insight into the mechanism by which HSV averts a short circuit in virion assembly by preventing the attachment of nascent nucleocapsids to NPCs and the delivery of their genomes back into the infected cell nucleus and, in doing so, have provided answers to a long-standing question in herpesvirus biology.

Automated summary

The expression of HSV pUL16 and pUL21 proteins can prevent nucleocapsids from binding to nuclear pore complexes and delivering their genomes back to the nucleus. This finding provides important insights into the biology of herpes simplex virus.