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Journal of Virology, September 2008, p. 9123-9133, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00289-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Single Amino Acid Residue Change in the P Protein of Parainfluenza Virus 5 Elevates Viral Gene Expression{triangledown}

Khalid A. Timani,1,{dagger} Dengyun Sun,2 Minghao Sun,3,{ddagger} Celia Keim,1,§ Yuan Lin,1 Phuong Tieu Schmitt,1 Anthony P. Schmitt,1,2,3,4 and Biao He1,2,3,4*

Department of Veterinary and Biomedical Sciences,1 Intercollege Graduate Program in Cell and Developmental Biology,2 Graduate Program in Pathobiology,3 Center of Molecular Immunology and Infectious Disease, Pennsylvania State University, University Park, Pennsylvania 168024

Received 8 February 2008/ Accepted 3 July 2008

Parainfluenza virus 5 (PIV5) is a prototypical paramyxovirus. The V/P gene of PIV5 encodes two mRNA species through a process of pseudotemplated insertion of two G residues at a specific site during transcription, resulting in two viral proteins, V and P, whose N termini of 164 amino acid residues are identical. Previously it was reported that mutating six amino acid residues within this identical region results in a recombinant PIV5 (rPIV5-CPI–) that exhibits elevated viral protein expression and induces production of cytokines, such as beta interferon and interleukin 6. Because the six mutations correspond to the shared region of the V protein and the P protein, it is not clear whether the phenotypes associated with rPIV5-CPI– are due to mutations in the P protein and/or mutations in the V protein. To address this question, we used a minigenome system and recombinant viruses to study the effects of mutations on the functions of the P and V proteins. We found that the P protein with six amino acid residue changes (Pcpi–) was more efficient than wild-type P in facilitating replication of viral RNA, while the V protein with six amino acid residue changes (Vcpi–) still inhibits minigenome replication as does the wild-type V protein. These results indicate that elevated viral gene expression in rPIV5-CPI– virus-infected cells can be attributed to a P protein with an increased ability to facilitate viral RNA synthesis. Furthermore, we found that a single amino acid residue change at position 157 of the P protein from Ser (the residue in the wild-type P protein) to Phe (the residue in Pcpi–) is sufficient for elevated viral gene expression. Using mass spectrometry and 33P labeling, we found that residue S157 of the P protein is phosphorylated. Based on these results, we propose that phosphorylation of the P protein at residue 157 plays an important role in regulating viral RNA replication.

* Corresponding author. Mailing address: Center of Molecular Immunology and Infectious Disease, Department of Veterinary and Biomedical Sciences, Pennsylvania State University, 115 Henning Bldg., University Park, PA 16802. Phone: (814) 863-8533. Fax: (814) 863-6140. E-mail: bxh40{at}psu.edu

{triangledown} Published ahead of print on 9 July 2008.

{dagger} Present address: Indiana University School of Medicine, Department of Microbiology and Immunology, R2 302, 950 W. Walnut St., Indianapolis, IN 46202.

{ddagger} Present address: Division of Oncovirology, Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037.

§ Present address: Department of Pathology & Cell Biology, Columbia University, 630 W. 168th Street, New York, NY 10032.

Journal of Virology, September 2008, p. 9123-9133, Vol. 82, No. 18
0022-538X/08/$08.00+0     doi:10.1128/JVI.00289-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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