This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, T. Articles by Ye, Z. Search for Related Content PubMed PubMed Citation Articles by Liu, T. Articles by Ye, Z.

 Previous Article  |  Next Article 

Journal of Virology, February 2005, p. 1918-1923, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1918-1923.2005

Attenuating Mutations of the Matrix Gene of Influenza A/WSN/33 Virus

Teresa Liu and Zhiping Ye^*

Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland

Received 2 August 2004/ Accepted 7 September 2004

The matrix protein (M1) of influenza virus plays an essential role in viral replication. Our previous studies have shown that basic amino acids 101RKLKR105 of M1 are involved in RNP binding and nuclear localization. For the present work, the functions of 101RKLKR105 were studied by introducing mutations into the M gene of influenza virus A/WSN/33 by reverse genetic methods. Individual substitution, R101S or R105S, had a minimal effect on viral replication. In contrast, the double mutation R101S-R105S was synergistic and resulted in temperature sensitivity reflected by reduced viral replication at a restrictive temperature. To investigate the in vivo effect on infection, BALB/c mice were infected with either A/WSN/33 wild-type (Wt) or mutant viruses and assessed for signs of illness, viral replication in the lungs, and survival rates. The results from mouse studies indicated that the R101S-R105S double mutant virus was strongly attenuated, while single mutant viruses R101S and R105S were minimally attenuated compared to A/WSN33 Wt under the same conditions. In challenge studies, mice immunized by infection with R101S-R105S were fully protected from lethal challenge with A/WSN/33. The replication and attenuating properties of R101S-R105S suggest its potential in development of live influenza virus vaccines.

---

* Corresponding author. Mailing address: Bldg. 29A, Rm. 2B17, 8800 Rockville Pike, Bethesda, MD 20982. Phone: (301) 435-5197. Fax: (301) 480-3157. E-mail: yez{at}cber.fda.gov.

---

Journal of Virology, February 2005, p. 1918-1923, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1918-1923.2005

This article has been cited by other articles:

• Wolk, K. E., Lazarowski, E. R., Traylor, Z. P., Yu, E. N. Z., Jewell, N. A., Durbin, R. K., Durbin, J. E., Davis, I. C. (2008). Influenza A Virus Inhibits Alveolar Fluid Clearance in BALB/c Mice. Am. J. Respir. Crit. Care Med. 178: 969-976 [Abstract] [Full Text]  
• Hui, E. K.-W., Smee, D. F., Wong, M.-H., Nayak, D. P. (2006). Mutations in Influenza Virus M1 CCHH, the Putative Zinc Finger Motif, Cause Attenuation in Mice and Protect Mice against Lethal Influenza Virus Infection.. J. Virol. 80: 5697-5707 [Abstract] [Full Text]  
• Berkhoff, E. G. M., de Wit, E., Geelhoed-Mieras, M. M., Boon, A. C. M., Symons, J., Fouchier, R. A. M., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2005). Functional Constraints of Influenza A Virus Epitopes Limit Escape from Cytotoxic T Lymphocytes. J. Virol. 79: 11239-11246 [Abstract] [Full Text]