The deubiquitylase-ubiquitin-specific protease 4 absence in HeLa cells leads to a reduction in Semliki Forest virus replication

Abstract

The emergence of a potential epidemic of alphaviruses is a growing concern for public health officials and the global community. These highly contagious and fast-spreading viruses have the potential to cause severe illness, disability, and even death, and are a growing threat to populations worldwide. Understanding the interaction between viruses, deubiquitylases (DUBs), and other human host cell proteins during replication is crucial when developing targeted antiviral medications. Many viruses have developed strategies to manipulate the host ubiquitin system by hijacking DUBs to evade the host immune response and promote viral replication, making DUBs attractive therapeutic targets. Small interfering RNA (siRNA) knockdown of USP4 expression inhibited Semliki Forest virus (SFV) replication and reduced virus titre. These findings highlight the potential to target USP4 as an antiviral treatment during alphavirus infection.