SLC35E1

SLC35E1 is an orphan transporter that participates in herpes simplex virus 1 (HSV-1) nuclear egress as a host factor required for efficient de-envelopment of perinuclear enveloped virions (PMID:35475666). It physically associates with the HSV-1 nuclear egress complex (NEC), binding the viral proteins UL34 and UL31 (PMID:35475666). Loss of SLC35E1 reduces HSV-1 replication and produces a de-envelopment defect characterized by aberrant membranous invaginations containing perinuclear enveloped virions, accumulation of virions in the perinuclear space, and mislocalization of the NEC (PMID:35475666). Beyond its role at the nuclear envelope during HSV-1 egress, no endogenous transport substrate or cellular function for SLC35E1 has been characterized in the available corpus.

1. 2022 Medium

   Establishing that the orphan transporter SLC35E1 is a physical partner of the HSV-1 nuclear egress machinery linked this previously uncharacterized protein to a defined viral process.

   Evidence Tandem affinity purification coupled with mass spectrometry in HSV-1-infected cells, detecting interaction with NEC components UL34 and UL31

   PMID:35475666

   Open questions at the time

   • Interaction mapped by affinity-MS without reciprocal validation or defined binding interface
   • Whether the association is direct or bridged by other factors is unresolved
   • No structural model of the SLC35E1–NEC contact
2. 2022 Medium

   Determining the functional consequence of SLC35E1 loss showed it is required for efficient de-envelopment, not merely a passive interactor of the NEC.

   Evidence CRISPR/Cas9 knockout with viral replication assays, emerin-based fluorescence reporter of NEC localization, and imaging of perinuclear virion accumulation

   PMID:35475666

   Open questions at the time

   • Mechanism by which SLC35E1 promotes de-envelopment is unknown
   • Whether transporter activity is required for the egress function was not tested
   • Single-lab finding without independent replication

• The endogenous transport substrate and the native (non-viral) cellular function of SLC35E1 remain undefined.
• No transported molecule identified
• No physiological role characterized outside HSV-1 infection
• Subcellular localization in uninfected cells not established in the corpus