SARS-CoV-2 Protein Nsp2 Stimulates Translation Under Normal and Hypoxic Conditions

Abstract

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 unknown. 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.

Modulation of various host cellular machinery during COVID‐19 infection

“…p38 MAPK pathway activates the MAP kinase‐interacting serine/threonine‐protein kinase (Mnk) that phosphorylates eIF4E 26 . Also, NSP2 was identified by proteomic analysis of SARS‐CoV2/human protein interaction, showing that it interacts with translation initiation factor eIF4E2 to promote viral protein synthesis and host proteins required for viral replication 25 …”