Key result
Leptomycin B inactivates CRM1 to drive immediate nuclear retention of equine arteritis virus nucleocapsid proteins.
The study reveals that the nucleocapsid protein of equine arteritis virus shuttles between the cytoplasm and nucleus using the CRM1-mediated export pathway prior to its role in cytoplasmic virus assembly.
Nuclear retention upon CRM1 blockade identifies shuttling in EAV; leaves open antiviral targeting in equine models.
RNA synthesis (genome replication and subgenomic mRNA transcription) directed by equine arteritis virus (EAV; family Arteriviridae, order Nidovirales) occurs on modified cytoplasmic membranes to which most viral replicase subunits localize. Remarkably, a fraction of non-structural protein 1 (nsp1), a protein essential for transcription but dispensable for genome replication, is present in the host cell nucleus, in particular during the earlier stages of infection. Expression of GFP-tagged fusion proteins revealed that nsp1 is actively imported into the nucleus. Although the signals responsible for nsp1 transport could not be identified, our studies revealed that another EAV protein with a partially nuclear localization, the nucleocapsid (N) protein, utilizes the CRM1-mediated nuclear export pathway. Inactivation of this pathway with the drug leptomycin B resulted in the unexpected and immediate nuclear retention of all N protein molecules, thus revealing that the protein shuttles between cytoplasm and nucleus before playing its role in cytoplasmic virus assembly.
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Tijms et al. (2002) studied Equine arteritis virus infection. Leptomycin B was evaluated on Nuclear localization and retention of viral proteins. Inactivation of the CRM1-mediated nuclear export pathway with leptomycin B resulted in the immediate nuclear retention of all equine arteritis virus nucleocapsid protein molecules.
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