HSV ICP27 hijacks host splicing factor SRSF3 to regulate pre-mRNA splicing and export for viral gene expression and immune evasion.
Level 5 - mechanism / opinion, no new human data
In vitro bench research and viral mutagenesis study
PubMed 41961905 · doi:10.1371/journal.ppat.1014146
What was done
The authors used viral mutagenesis and molecular biology assays to investigate how the herpes simplex virus (HSV) immediate early protein ICP27 inhibits co-transcriptional splicing. They examined the interaction of ICP27 with host serine/arginine-rich splicing factor 3 (SRSF3) and nuclear RNA export factor 1 (NXF1), tested the phenotypic effects of mutating the ICP27 N-terminal nuclear export signal and RGG RNA-binding domain, and assessed the impact of knocking down the U1 snRNP component U1-70K.
What was found
No quantitative values, effect sizes, or statistical metrics were reported in the abstract. Qualitatively, ICP27 inhibited pre-mRNA splicing by binding host SRSF3 at an exonic motif near the 5' splice site independently of the RGG domain, and promoted NXF1-mediated nuclear export of unspliced transcripts. Dual mutation of the ICP27 nuclear export signal and RGG domain impaired splicing inhibition, reduced ICP27-dependent gene expression, and restricted viral growth. Knockdown of U1-70K inhibited splicing and enhanced the expression of ICP27-dependent genes.
Why it matters
This study defines how HSV manipulates host splicing and export machinery to regulate gene expression during active replication, providing a mechanistic basis for how viral transcript processing might be restricted during latency.
Limits
The abstract reports no numerical data, effect sizes, sample sizes, or error bounds. Findings are limited to in vitro molecular and viral systems, and the proposed role in latency and immune evasion remains an unverified hypothesis.
Cited by
- contradicts In the cell, mRNA remains in the cytoplasm and does not enter the nucleus.