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Journal of Virology, November 2005, p. 13943-13952, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13943-13952.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Overexpression of the M2-2 Protein of Respiratory Syncytial Virus Inhibits Viral Replication

Xing Cheng, HyunJung Park, Helen Zhou, and Hong Jin*

MedImmune Vaccines Inc., 297 North Bernardo Ave., Mountain View, California 94043

Received 12 May 2005/ Accepted 9 August 2005

The M2-2 protein of respiratory syncytial virus (RSV) is involved in regulation of viral RNA transcription and replication. Encoded by the next-to-last gene of RSV, the M2-2 open reading frame (ORF) overlaps with the upstream M2-1 ORF, suggesting that the production of the M2-2 protein might be tightly regulated during virus replication. To evaluate the effect of M2-2 overexpression on RSV replication, the M2-2 gene was separated from M2-1 by leaving it at the position prior to the M2-1 or moving it to the promoter proximal position as an independent transcriptional unit in the RSV A2 genome. Although recombinant viruses bearing the shuffled M2-2 gene were recovered and expressed higher levels of M2-2, most of these viruses grew poorly in HEp-2 cells. Sequence analysis revealed that various mutations (substitution, insertion, and deletion) occurred in the M2-2 gene, resulting in reduced M2-2 activity as measured by the RSV minigenome system. Further examination of the M2-2 sequence and its function showed that either one of the first two AUG codons located at the 5' end of M2-2 could be used to produce a functional M2-2 protein and that deletion of the first six amino acids from its N terminus or four amino acids from its C terminus greatly reduced its function. The effect of M2-2 protein on RSV replication was also studied by examining RSV replication in cells transiently expressing M2-2. The M2-2 protein expressed at a high level completely inhibited RSV replication. These results strongly suggested that the level of the M2-2 protein produced in the infected cells is critical to RSV replication.

* Corresponding author. Mailing address: MedImmune Vaccines Inc., 297 N. Bernardo Ave., Mountain View, CA 94043. Phone: (650) 603-2367. Fax: (650) 603-3367. E-mail: jinh{at}medimmune.com.

Journal of Virology, November 2005, p. 13943-13952, Vol. 79, No. 22
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.22.13943-13952.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Cowton, V. M., McGivern, D. R., Fearns, R. (2006). Unravelling the complexities of respiratory syncytial virus RNA synthesis. J. Gen. Virol. 87: 1805-1821 [Abstract] [Full Text]  


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