Respiratory syncytial virus small hydrophobic protein (SH protein)

The Respiratory syncytial virus small hydrophobic protein (SH protein) is a short, type II transmembrane protein (64 amino acids) encoded by the RSV genome. The protein oligomerizes into pentamers and forms pH-dependent, acid-activated ion channels (viroporin activity) in host cell membranes, specifically displaying proton and monovalent cation flux. SH protein suppresses apoptosis via inhibition of TNF-α signaling, contributes to immune evasion and RSV pathogenesis, and modulates host cytokine responses such as IL-1β through inflammasome activation. Its absence does not block virus replication or syncytium formation in vitro, but leads to attenuated viral phenotype and diminished pathogenicity in vivo, including reduced lung viral titers and enhanced immune activation. SH accumulates at the Golgi apparatus in infected cells and may facilitate virus release by modifying the secretory pathway. The SH protein is a validated antiviral drug target, with small-molecule inhibitors able to block its channel activity.

Other names

SH proteinRSV SHHuman respiratory syncytial virus SH proteinSmall hydrophobic protein of RSV

Inhibitors such as pyronin B block SH-mediated ion channel activity in viral and host membranes.