Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1

AUTOR(ES)

Neumann, Gabriele

FONTE

Oxford University Press

RESUMO

For nuclear export of proteins, the formation of a ternary export complex composed of the export substrate, a cellular export factor and Ran-GTP is crucial. CRM1 is a cellular export factor for proteins containing leucine-rich nuclear export signals (NESs). Although the NES sequence is crucial for nuclear export, its exact role in the formation of the ternary export complex is controversial. Here we demonstrate an interaction between human CRM1 (hCRM1) and influenza A virus NS2 protein, which contains an NES motif in its N-terminal region. Replacement of the hydrophobic amino acids in the NES motif did not abolish NS2’s interaction with hCRM1. Using our recently established systems for the generation of influenza virus or virus-like particles from cloned cDNAs, we found that NS2 is essential for nuclear export of influenza virus ribonucleoprotein (RNP) complexes, and that alteration of the NS2-NES abrogated this event and influenza virus generation. These findings suggest that the NS2-NES is not crucial for the interaction of this protein with hCRM1, but is for the formation of the ternary export complex with Ran-GTP.

Documentos Relacionados

• Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)
• A masked NES in INI1/hSNF5 mediates hCRM1-dependent nuclear export: implications for tumorigenesis
• Nuclear Export Factor CRM1 Interacts with Nonstructural Proteins NS2 from Parvovirus Minute Virus of Mice
• Interaction between Parvovirus NS2 Protein and Nuclear Export Factor Crm1 Is Important for Viral Egress from the Nucleus of Murine Cells
• Generation of Influenza A Virus NS2 (NEP) Mutants with an Altered Nuclear Export Signal Sequence