The respiratory syncytial virus M2-2 protein is targeted for proteasome degradation and inhibits translation and stress granules assembly

Author(s)

Scudero, Orlando Bonito ; Santiago, Veronica Feijoli ; Palmisano, Giuseppe ; Simabuco, Fernando Moreira ; Ventura, Armando Morais

• Document type: Journal article
• Source: PLoS One; v. 18, n. 7, p. 26-pg., 2023-07-25.

Abstract

The M2-2 protein from the respiratory syncytial virus (RSV) is a 10 kDa protein expressed by the second ORF of the viral gene M2. During infection, M2-2 has been described as the polymerase cofactor responsible for promoting genome replication, which occurs by the induction of changes in interactions between the polymerase and other viral proteins at early stages of infection. Despite its well-explored role in the regulation of the polymerase activity, little has been made to investigate the relationship of M2-2 with cellular proteins. A previous report showed poor recruitment of M2-2 to viral structures, with the protein being mainly localized to the nucleus and cytoplasmic granules. To unravel which other functions M2-2 exerts during infection, we performed proteomic analysis of co-immunoprecipitated cellular partners, identifying enrichment of proteins involved with regulation of translation, protein folding and mRNA splicing. In approaches based on these data, we found that M2-2 expression downregulates eiF2 & alpha; phosphorylation and inhibits both translation and stress granules assembly. Finally, we also verified that M2-2 is targeted for proteasome degradation, being localized to granules composed of defective ribosomal products at the cytoplasm. These results suggest that besides its functions in the replicative complex, M2-2 may exert additional functions to contribute to successful RSV infection. (AU)

• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/50299-2 - Chasing cellular partners of respiratory syncytial virus
• Grantee: Armando Morais Ventura
• Support Opportunities: Regular Research Grants