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Journal of Virology, November 2007, p. 12111-12118, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00560-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interferons and Ribavirin Effectively Inhibit Norwalk Virus Replication in Replicon-Bearing Cells{triangledown}

Kyeong-Ok Chang* and David W. George

Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, Kansas 66506

Received 16 March 2007/ Accepted 24 August 2007

The development of effective therapies for noroviral gastroenteritis has been hampered by the absence of a cell culture system. Recently, we reported the generation of Norwalk virus (NV) replicon-bearing cells in BHK21 and Huh-7 cells and demonstrated that alpha interferon (IFN-{alpha}) effectively inhibited the replication of NV in these cells. In continuing studies for screening potential antinoroviral agents, we tested IFN-{gamma} and ribavirin for their effects on NV replication in the cells. Like IFN-{alpha}, IFN-{gamma} inhibited the replication of NV in the replicon-bearing cells, showing the reduction of the NV genome and proteins in a dose-dependent manner. The effective dose for reducing 50% (ED50) of the NV genome and protein was calculated to be approximately 40 units/ml. When ribavirin was applied to the cells, it effectively reduced the NV genome and protein with the ED50 calculated as approximately 40 µM. The combination of IFN-{alpha} and ribavirin showed additive effects on the inhibition of NV replication. With the addition of guanosine to the ribavirin treatment, moderately reversed antiviral effects were observed, suggesting that the ribavirin effect may be associated with the depletion of GTP in the cells. Sequencing analysis of the conserved polymerase regions of NV in the ribavirin-treated (100 µM) and nontreated groups showed that the mutation rates were similar and indicated that ribavirin did not induce catastrophic mutations. The NV replicon-bearing cells provide an excellent tool for screening potential antinoroviral agents, and our results indicated that IFNs and ribavirin may be good therapeutic options for noroviral gastroenteritis.

* Corresponding author. Mailing address: Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506. Phone: (785) 532-3849. Fax: (785) 532-4039. E-mail: kchang{at}vet.ksu.edu

{triangledown} Published ahead of print on 12 September 2007.

Journal of Virology, November 2007, p. 12111-12118, Vol. 81, No. 22
0022-538X/07/$08.00+0     doi:10.1128/JVI.00560-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Glass, R. I., Parashar, U. D., Estes, M. K. (2009). Norovirus Gastroenteritis. NEJM 361: 1776-1785 [Full Text]  
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  • Cannon, J. L., Lindesmith, L. C., Donaldson, E. F., Saxe, L., Baric, R. S., Vinje, J. (2009). Herd Immunity to GII.4 Noroviruses Is Supported by Outbreak Patient Sera. J. Virol. 83: 5363-5374 [Abstract] [Full Text]  
  • Changotra, H., Jia, Y., Moore, T. N., Liu, G., Kahan, S. M., Sosnovtsev, S. V., Karst, S. M. (2009). Type I and Type II Interferons Inhibit the Translation of Murine Norovirus Proteins. J. Virol. 83: 5683-5692 [Abstract] [Full Text]  
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