Sequestration Strikes Again: Rotavirus-Induced Accumulation of Cellular Transcripts in the Nucleus Inhibits Host Protein Translation

Abstract

Evaluation of: Rubio RM, Mora SI, Romero P, Arias CF, López S. Rotavirus prevents the expression of host responses by blocking the nucleocytoplasmic transport of polyadenylated mRNAs. J. Virol. 87(11), 6336–6345 (2013). Rotaviruses are a leading cause of pediatric diarrhea worldwide and are estimated to be responsible for approximately 450,000 deaths each year. Although the incidence of severe diarrhea induced by rotavirus has fallen sharply in developed countries due to the introduction of vaccines, it remains a leading cause of diarrhea leading to death in low-income countries. A key feature of rotavirus replication is the robust production of viral proteins and simultaneous inhibition of host protein synthesis in infected cells. Studies have shown an accumulation of cytoplasmic poly(A)-binding protein (PABPC) in the nucleus of rotavirus-infected cells, but the consequences of this were unknown. Here, Rubio and colleagues show that the nuclear accumulation of PABPC inhibits the export of polyadenylated host mRNAs to the cytoplasm, thereby preventing their translation. The viral nonstructural protein NSP3 is responsible for the observed increase of PABPC and poly(A)-containing mRNAs in the nucleus of infected cells. If introduced directly into the cytoplasm of infected cells, polyadenylated mRNAs are efficiently translated, suggesting there is not a preferential translation of viral mRNAs over cellular mRNAs once they are in the cytoplasm. The results presented demonstrate that the prevention of polyadenylated mRNA export from the nucleus of infected cells is an important strategy to inhibit host translation, and probably works in concert with other viral strategies to prevent the translation of host proteins.