Human cytomegalovirus antagonizes SMC5/6 driven genome silencing via UL35 instituted proteasomal degradation of SLF2.

HCMV UL35 protein promotes proteasomal degradation of SLF2, disrupting SMC5/6 complex recruitment to PML nuclear bodies during infection.

• Why it matters: Understanding how viruses evade host genome silencing mechanisms is crucial for developing antiviral strategies. SMC5/6 acts as a restriction factor by silencing episomal DNA, but viruses have evolved countermeasures.
• What they did: Researchers examined SMC5/6 components during HCMV infection and identified UL35 as necessary and sufficient for degrading SLF2 via the proteasome, using infection models, mutant viruses, and siRNA depletion.
• The result: UL35-mediated SLF2 degradation prevents SMC5/6 from silencing viral genomes, enabling efficient immediate early gene expression and viral replication, revealing UL35 as a novel viral antagonist of genome silencing.