The journey of herpesvirus capsids and genomes to the host cell nucleus

Starting a herpesviral infection is a steeplechase across membranes, cytosol, and nuclear envelopes and against antiviral defence mechanisms. Here, we highlight recent insights on capsid stabilization at the portals during assembly, early capsid-host interactions ensuring nuclear targeting of incoming capsids, and genome uncoating. After fusion with a host membrane, incoming capsids recruit microtubule motors for traveling to the centrosome, and by unknown mechanisms get forward towards the nucleus. The interaction of capsid-associated tegument proteins with nucleoporins orients the capsid portal towards the nuclear pore, and presumably after removal of the portal caps the genomes that have been packaged under pressure can be injected into the nucleoplasm for transcription and replication. Some cell types disarm the incoming capsids or silence the incoming genomes to reduce the likelihood of infection.

Automated summary

This article highlights the key steps in herpesviral infection, including capsid stabilization during assembly, early interactions with host cells to ensure nuclear targeting, and genome uncoating. After fusion with a host membrane, capsids recruit microtubule motors for traveling to the centrosome, eventually reaching the nucleus. Capsid-associated tegument proteins interact with nucleoporins to facilitate injection of genomes into the nucleoplasm for transcription and replication, while some cell types may disarm or silence incoming capsids to prevent infection.