SARS-CoV-2 viral protein Nsp2 stimulates translation under normal and hypoxic conditions

When viruses like SARS-CoV-2 infect cells, they reprogram the repertoire of cellular and viral transcripts that are being translated to optimize their strategy of replication, often targeting host translation initiation factors, particularly eIF4F complex consisting of eIF4E, eIF4G and eIF4A. A proteomic analysis of SARS-CoV-2/human proteins interaction revealed viral Nsp2 and initiation factor eIF4E2, but a role of Nsp2 in regulating translation is still controversial. HEK293T cells stably expressing Nsp2 were tested for protein synthesis rates of synthetic and endogenous mRNAs known to be translated via cap- or IRES-dependent mechanism under normal and hypoxic conditions. Both cap- and IRES-dependent translation were increased in Nsp2-expressing cells under normal and hypoxic conditions, especially mRNAs that require high levels of eIF4F. This could be exploited by the virus to maintain high translation rates of both viral and cellular proteins, particularly in hypoxic conditions as may arise in SARS-CoV-2 patients with poor lung functioning.

Automated summary

When infecting cells, viruses like SARS-CoV-2 alter the translation of cellular and viral transcripts to enhance their replication. They target host translation initiation factors, particularly the eIF4F complex, consisting of eIF4E, eIF4G, and eIF4A. A study found that Nsp2 of SARS-CoV-2 interacts with eIF4E2, which may play a role in translation regulation. Nsp2 expression in cells increased both cap- and IRES-dependent translation, especially for mRNAs requiring high levels of eIF4F.