Plasma Membrane Profiling of HSV-1 infected i3Neurones

ABSTRACT: Herpes simplex virus (HSV)-1 invasion of the CNS can cause life-threatening herpes simplex encephalitis, the most common infectious encephalitis worldwide. The molecular consequences of lytic infection in CNS neurones are poorly understood, and many viral proteins remain functionally uncharacterised in this context. To investigate HSV-1 infection in human cortical neurones, a scalable induced pluripotent stem cell (i3 iPSC) system that generates human cortical glutamatergic neurones was used. Proteomic analysis in keratinocytes has previously identified the HSV-1 protein pUL56 as a major regulator of the surface proteome, contributing to immune evasion. Given the diversity of proteins present on the plasma membrane of neurones versus keratinocytes, it was hypothesised that pUL56 would have alternate functions in infected neurones. To determine the role of pUL56 in infected-neurones, plasma membrane proteomics (PMP) of wild-type (WT) and ΔpUL56 HSV-1 infected i3Neurones was performed, revealing extensive remodelling of the neuronal surface during infection, including reduced abundance of proteins involved in cell adhesion, activin receptor signalling, and voltage-gated ion channel activity. This analysis revealed that pUL56 was specifically responsible for the removal of voltage-gated sodium, potassium and calcium ion channels from the plasma membrane.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cerebral Cortex Neuron, Brain, Cell Culture, Electrically Active Cell

SUBMITTER: Stephen Graham  

LAB HEAD: Stephen Charles Graham

PROVIDER: PXD076394 | Pride | 2026-10-16

REPOSITORIES: Pride