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Journal of Virology, December 2002, p. 13055-13061, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13055-13061.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Restriction of Viral Replication by Mutation of the Influenza Virus Matrix Protein

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 20892

Received 16 July 2002/ Accepted 4 September 2002

The matrix protein (M1) of influenza virus plays an essential role in viral assembly and has a variety of functions, including association with influenza virus ribonucleoprotein (RNP). Our previous studies show that the association of M1 with viral RNA and nucleoprotein not only promotes formation of helical RNP but also is required for export of RNP from the nucleus during viral replication. The RNA-binding domains of M1 have been mapped to two independent regions: a zinc finger motif at amino acid positions 148 to 162 and a series of basic amino acids (RKLKR) at amino acid positions 101 to 105, which is also involved in RNP-binding activity. To further understand the role of the RNP-binding domain of M1 in viral assembly and replication, mutations in the coding sequences of RKLKR and the zinc finger motif of M1 were constructed using a PCR technique and introduced into wild-type influenza virus by reverse genetics. Altering the zinc finger motif of M1 only slightly affected viral growth. Substitution of Arg with Ser at position 101 or 105 of RKLKR did not have a major impact on nuclear export of RNP or viral replication. In contrast, deletion of RKLKR or substitution of Lys with Asn at position 102 or 104 of RKLKR resulted in a lethal mutation. These results indicate that the RKLKR domain of M1 protein plays an important role in viral replication.

* Corresponding author. Mailing address: Laboratory of Pediatric and Respiratory Viral Diseases, Division of Viral Products, Food and Drug Administration, 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, December 2002, p. 13055-13061, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.13055-13061.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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