Respiratory syncytial virus transcription anti-termination protein M2-1 (M2-1)

Respiratory syncytial virus transcription anti-termination protein M2-1 (M2-1) is a 194-amino acid tetrameric protein of HRSV, primarily functioning as a transcriptional anti-terminator that ensures viral polymerase processivity and the synthesis of full-length mRNA transcripts. It contains a zinc finger domain at its N-terminus, an oligomerization domain, and a globular core, each contributing to its interaction with viral RNA and the phosphoprotein P. M2-1 binds nascent polyA-rich viral mRNAs in cytoplasmic inclusion bodies, stabilizes the transcriptase complex, and regulates mRNA maturation, translation, and stabilization. Disruption of M2-1 function severely impairs viral replication, making it a critical target for antiviral research. M2-1 is also subject to dynamic phosphorylation at specific serine residues, which modulates its activity and interaction with cellular and viral factors. M2-1 is essential and specific for RSV transcription, not needed for genomic replication or for other pneumoviruses. It interacts dynamically with the phosphoprotein P and viral mRNA through partially overlapping binding sites, which may be mutually exclusive. Its preferred RNA binding is to polyA-rich regions, related to the synthesis and stabilization of viral mRNA. Genetic or pharmacologic disruption of M2-1 abolishes RSV mRNA synthesis, confirming therapeutic target status. M2-1 has no equivalent human homolog, reducing the risk of target-related human toxicity.

Other names

Respiratory syncytial virus M2-1 proteinHRSV M2-1

Inhibitors targeting M2-1 are expected to block anti-termination activity, resulting in truncated viral transcripts and non-productive RSV infection.