Highly Basic Clusters in the Herpes Simplex Virus 1 Nuclear Egress Complex Drive Membrane Budding by Inducing Lipid Ordering

Published

August 24, 2021

Author(s)

Michael K. Thorsen, Alex Lai, Michelle W. Lee, David Hoogerheide, Gerard C. Wong, Jack H. Freed, Ekaterina Heldwein

Abstract

During replication of herpesviruses, capsids escape from the nucleus into the cytoplasm by budding at the inner nuclear membrane. This process is mediated by the viral nuclear egress complex (NEC), but how the NEC interacts with lipids or generates membrane curvature necessary for budding is unclear. Here, by combining different biophysical approaches, we show that the membrane-interacting regions of the HSV-1 NEC promote two different types of membrane curvature: the negative mean curvature and the negative Gaussian curvature necessary for the formation of the bud and scission of the neck of the bud, respectively. NEC-mediated membrane budding requires clusters of positively charged residues and is inhibited by pseudophosphorylation, which introduces negative charges. The virus may thus use phosphorylation to control NEC/membrane interactions and membrane-budding activity of the NEC. We propose that the NEC is an intrinsically multifunctional membrane-budding machine that orchestrates membrane remodeling necessary for herpesvirus nuclear egress.

Citation

mBio

Volume

12

Issue

4

Pub Type

Journals

Keywords

HSV-1, nuclear egress, membrane interactions, membrane budding, membrane curvature, electron spin resonance, neutron reflectometry, small-angle X-ray scattering

Citation

Thorsen, M. , Lai, A. , Lee, M. , Hoogerheide, D. , Wong, G. , Freed, J. and Heldwein, E. (2021), Highly Basic Clusters in the Herpes Simplex Virus 1 Nuclear Egress Complex Drive Membrane Budding by Inducing Lipid Ordering, mBio (Accessed October 22, 2025)