Respiratory syncytial virus small hydrophobic protein (SH protein) (RSV SH)

The Respiratory syncytial virus small hydrophobic protein (SH protein) is a 64-65 amino acid type II transmembrane protein that functions as a viroporin (UniProt P03425). It oligomerizes within the host cell membrane to form pentameric, cation-selective ion channels that alter membrane permeability and facilitate viral processes (Gan et al., 2012, Protein & Cell). While the SH protein is not strictly required for viral replication in vitro, it is a critical virulence factor that modulates the host immune response by inhibiting TNF-alpha-induced apoptosis and activating the NLRP3 inflammasome (Triantafilou et al., 2013, Scientific Reports). These activities help the virus evade host defenses and contribute to the inflammatory damage observed in RSV-related bronchiolitis and pneumonia. As a therapeutic target, the SH protein is susceptible to inhibition by small molecules such as hexamethylene amiloride (HMA), which block the ion channel pore and disrupt its function (Fuentes et al., 2007, FEBS Letters). However, no SH-targeted therapies are currently approved for clinical use, and development faces challenges related to viral resistance and the need for high selectivity against host ion channels.

Other names

SH proteinSmall hydrophobic proteinViroporin SHRSV SH

Inhibition of pentameric ion channel activity and disruption of viral pore formation in host cell membranes (Fuentes et al., 2007; Gan et al., 2012).