Getting to and through the inner nuclear membrane during herpesvirus nuclear egress

•Egress of herpesvirus capsids from the nucleus is a fascinating, multi-step process.•How herpesvirus capsids move from nuclear interior to nuclear rim is controversial.•The structurally conserved nuclear egress complex (NEC) exhibits unusual features.•Budding through the inner nuclear membrane entails hexameric NEC lattice formation.

Herpesviruses, like most DNA viruses, replicate and package their genomes into capsids in the host cell nucleus. Capsids then transit to the cytoplasm in a fascinating process called nuclear egress, which includes several unusual steps: Movement of capsids from the nuclear interior to the periphery, disruption of the nuclear lamina, capsid budding through the inner nuclear membrane, and fusion of enveloped particles with the outer nuclear membrane. Here, we review recent advances and emerging questions relating to herpesvirus nuclear egress, emphasizing controversies regarding mechanisms for capsid trafficking to the nuclear periphery, and implications of recent structures of the two-subunit, viral nuclear egress complex for the process, particularly at the step of budding through the inner nuclear membrane.

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