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Journal of Virology, August 2001, p. 7375-7383, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7375-7383.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Influenza B and C Virus NEP (NS2) Proteins Possess Nuclear Export Activities

Jason Paragas, Julie Talon,dagger Robert E. O'Neill,Dagger D. Karl Anderson, Adolfo García-Sastre, and Peter Palese*

Department of Microbiology, Mount Sinai School of Medicine, New York University, New York, New York 10029

Received 23 January 2001/Accepted 16 May 2001

Nucleocytoplasmic transport of viral ribonucleoproteins (vRNPs) is an essential aspect of the replication cycle for influenza A, B, and C viruses. These viruses replicate and transcribe their genomes in the nuclei of infected cells. During the late stages of infection, vRNPs must be exported from the nucleus to the cytoplasm prior to transport to viral assembly sites on the cellular plasma membrane. Previously, we demonstrated that the influenza A virus nuclear export protein (NEP, formerly referred to as the NS2 protein) mediates the export of vRNPs. In this report, we suggest that for influenza B and C viruses the nuclear export function is also performed by the orthologous NEP proteins (formerly referred to as the NS2 protein). The influenza virus B and C NEP proteins interact in the yeast two-hybrid assay with a subset of nucleoporins and with the Crm1 nuclear export factor and can functionally replace the effector domain from the human immunodeficiency virus type 1 Rev protein. We established a plasmid transfection system for the generation of virus-like particles (VLPs) in which a functional viral RNA-like chloramphenicol acetyltransferase (CAT) gene is delivered to a new cell. VLPs generated in the absence of the influenza B virus NEP protein were unable to transfer the viral RNA-like CAT gene to a new cell. From these data, we suggest that the nuclear export of the influenza B and C vRNPs are mediated through interaction between NEP proteins and the cellular nucleocytoplasmic export machinery.

* Corresponding author. Mailing address: Department of Microbiology, Mount Sinai School of Medicine, New York University, 1 Gustave L. Levy Place, New York, NY 10029. Phone: (212) 241-7318. Fax: (212) 722-3634. E-mail: peter.palese{at}mssm.edu.

dagger Present address: Center for the Study of Hepatitis C, Department of Virology and Infectious Disease, Rockefeller University, New York, NY 10021.

Dagger Present address: Wyeth Lederle Vaccines, Pearl River, NY 10965.

Journal of Virology, August 2001, p. 7375-7383, Vol. 75, No. 16
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.16.7375-7383.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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