SARS-CoV-2 and MERS-CoV disrupt host protein synthesis via nsp1 with differential effects on the integrated stress response - PubMed
3 hours ago
- #Coronavirus
- #Host Protein Synthesis
- #Integrated Stress Response
- SARS-CoV-2 activates host integrated stress response (ISR) kinases PKR and PERK, leading to eIF2α phosphorylation and inhibition of host protein synthesis.
- MERS-CoV infection does not result in eIF2α phosphorylation, indicating differential interactions with the ISR compared to SARS-CoV-2.
- Both SARS-CoV-2 and MERS-CoV use the conserved nonstructural protein 1 (nsp1) to disrupt host protein synthesis and promote host mRNA degradation.
- Mutations in nsp1 of SARS-CoV-2 rescue translation in PERK knockout cells but not in wildtype or PKR knockout cells, while analogous mutations in MERS-CoV nsp1 rescue translation even in wildtype cells.
- SARS-CoV-2 wildtype suppresses GADD34 expression, a negative regulator of eIF2α phosphorylation, whereas SARS-CoV-2 nsp1 mutants and MERS-CoV wildtype induce GADD34.