RNA synthesis regulatory protein M2-2 (M2-2) (M2-2)

The RNA synthesis regulatory protein M2-2 is a small, basic protein of approximately 90 amino acids encoded by the second open reading frame (ORF2) of the M2 gene in Respiratory Syncytial Virus (RSV) (UniProt P04545). It functions as a pivotal regulatory switch that balances the transition from viral mRNA transcription to genomic RNA replication during the viral life cycle (Bermingham & Collins, 1999, PMID: 10559318). In the early stages of infection, transcription predominates; however, as M2-2 protein levels accumulate, it suppresses further transcription and promotes the synthesis of genomic and antigenomic RNA required for virion assembly. Viruses lacking the M2-2 protein exhibit a unique phenotype characterized by increased viral gene expression but severely restricted replication, making them ideal candidates for live-attenuated vaccines (Teng et al., 2000, PMID: 10623771). Clinical studies of M2-2-deleted RSV strains, such as RSV ΔM2-2, have demonstrated that these candidates are highly attenuated in seronegative children while remaining strongly immunogenic due to high antigen production (Karron et al., 2015, PMID: 25653445). Beyond its role in RNA synthesis, M2-2 also contributes to viral evasion of the host immune system by antagonizing the induction of type I interferons (Ling et al., 2009, PMID: 19158245). Consequently, M2-2 is a primary target for genetic engineering in vaccine development and a potential target for novel antiviral therapies aimed at disrupting the viral replication cycle.

Other names

Respiratory syncytial virus M2-2 proteinM2 ORF2 proteinRSV M2-2Transcription/replication regulatory protein M2-2

Deletion or silencing of the M2-2 protein results in viral attenuation by shifting the balance of viral RNA synthesis toward excessive mRNA transcription and away from genome replication, leading to high antigen expression with minimal production of infectious progeny.