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Journal of Virology, January 2008, p. 105-114, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01520-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Akt Plays a Critical Role in Replication of Nonsegmented Negative-Stranded RNA Viruses{triangledown}

Minghao Sun,1,{dagger} Sandra M. Fuentes,1,{dagger} Khalid Timani,2 Dengyun Sun,3 Chris Murphy,2 Yuan Lin,2 Avery August,1,2,3,4 Michael N. Teng,1,3,4,5 and Biao He1,2,3,4*

Graduate Program in Pathobiology,1 Department of Veterinary and Biomedical Sciences,2 Intercollege Graduate Program in Cell and Developmental Biology,3 Center of Molecular Immunology and Infectious Disease,4 Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 168025

Received 11 July 2007/ Accepted 10 October 2007

The order Mononegavirales (comprised of nonsegmented negative-stranded RNA viruses or NNSVs) contains many important pathogens. Parainfluenza virus 5 (PIV5), formerly known as simian virus 5, is a prototypical paramyxovirus and encodes a V protein, which has a cysteine-rich C terminus that is conserved among all paramyxoviruses. The V protein of PIV5, like that of many other paramyxoviruses, plays an important role in regulating viral RNA synthesis. In this work, we show that V interacts with Akt, a serine/threonine kinase, also known as protein kinase B. Both pharmacological inhibitors and small interfering RNA against Akt1 reduced PIV5 replication, indicating that Akt plays a critical role in PIV5 replication. Furthermore, treatment with Akt inhibitors also reduced the replication of several other paramyxoviruses, as well as vesicular stomatitis virus, the prototypical rhabdovirus, indicating that Akt may play a more universal role in NNSV replication. The phosphoproteins (P proteins) of NNSVs are essential cofactors for the viral RNA polymerase complex and require heavy phosphorylation for their activity. Inhibition of Akt activity reduced the level of P phosphorylation, suggesting that Akt is involved in regulating viral RNA synthesis. In addition, Akt1 phosphorylated a recombinant P protein of PIV5 purified from bacteria. The finding that Akt plays a critical role in replication of NNSV will lead to a better understanding of how these viruses replicate, as well as novel strategies to treat infectious diseases caused by NNSVs.

* 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 24 October 2007.

{dagger} M.S. and S.M.F. contributed equally.

Journal of Virology, January 2008, p. 105-114, Vol. 82, No. 1
0022-538X/08/$08.00+0     doi:10.1128/JVI.01520-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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