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 Park, M.-S. Articles by Palese, P. Search for Related Content PubMed PubMed Citation Articles by Park, M.-S. Articles by Palese, P.

 Previous Article  |  Next Article 

Journal of Virology, September 2003, p. 9522-9532, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9522-9532.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Newcastle Disease Virus V Protein Is a Determinant of Host Range Restriction

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029

Received 8 April 2003/ Accepted 3 June 2003

It has been demonstrated that the V protein of Newcastle disease virus (NDV) functions as an alpha/beta interferon (IFN-/ß) antagonist (M. S. Park, M. L. Shaw, J. Muñoz-Jordan, J. F. Cros, T. Nakaya, N. Bouvier, P. Palese, A. García-Sastre, and C. F. Basler, J. Virol. 77:1501-1511, 2003). We now show that the NDV V protein plays an important role in host range restriction. In order to study V functions in vivo, recombinant NDV (rNDV) mutants, defective in the expression of the V protein, were generated. These rNDV mutants grow poorly in both embryonated chicken eggs and chicken embryo fibroblasts (CEFs) compared to the wild-type (wt) rNDV. However, insertion of the NS1 gene of influenza virus A/PR8/34 into the NDV V(-) genome [rNDV V(-)/NS1] restores impaired growth to wt levels in embryonated chicken eggs and CEFs. These data indicate that for viruses infecting avian cells, the NDV V protein and the influenza NS1 protein are functionally interchangeable, even though there are no sequence similarities between the two proteins. Interestingly, in human cells, the titer of wt rNDV is 10 times lower than that of rNDV V(-)/NS1. Correspondingly, the level of IFN secreted by human cells infected with wt rNDV is much higher than that secreted by cells infected with the NS1-expressing rNDV. This suggests that the IFN antagonist activity of the NDV V protein is species specific. Finally, the NDV V protein plays an important role in preventing apoptosis in a species-specific manner. The rNDV defective in V induces apoptotic cell death more rapidly in CEFs than does wt rNDV. Taken together, these data suggest that the host range of NDV is limited by the ability of its V protein to efficiently prevent innate host defenses, such as the IFN response and apoptosis.

This article has been cited by other articles:

• Bartlett, E. J., Hennessey, M., Skiadopoulos, M. H., Schmidt, A. C., Collins, P. L., Murphy, B. R., Pickles, R. J. (2008). Role of Interferon in the Replication of Human Parainfluenza Virus Type 1 Wild Type and Mutant Viruses in Human Ciliated Airway Epithelium. J. Virol. 82: 8059-8070 [Abstract] [Full Text]  
• Munoz-Fontela, C., Macip, S., Martinez-Sobrido, L., Brown, L., Ashour, J., Garcia-Sastre, A., Lee, S. W., Aaronson, S. A. (2008). Transcriptional role of p53 in interferon-mediated antiviral immunity. J. Exp. Med. 205: 1929-1938 [Abstract] [Full Text]  
• Nishio, M., Ohtsuka, J., Tsurudome, M., Nosaka, T., Kolakofsky, D. (2008). Human Parainfluenza Virus Type 2 V Protein Inhibits Genome Replication by Binding to the L Protein: Possible Role in Promoting Viral Fitness. J. Virol. 82: 6130-6138 [Abstract] [Full Text]  
• Yount, J. S., Gitlin, L., Moran, T. M., Lopez, C. B. (2008). MDA5 Participates in the Detection of Paramyxovirus Infection and Is Essential for the Early Activation of Dendritic Cells in Response to Sendai Virus Defective Interfering Particles. J. Immunol. 180: 4910-4918 [Abstract] [Full Text]  
• Zhu, Q., Yang, H., Chen, W., Cao, W., Zhong, G., Jiao, P., Deng, G., Yu, K., Yang, C., Bu, Z., Kawaoka, Y., Chen, H. (2008). A Naturally Occurring Deletion in Its NS Gene Contributes to the Attenuation of an H5N1 Swine Influenza Virus in Chickens. J. Virol. 82: 220-228 [Abstract] [Full Text]  
• Vigil, A., Park, M.-S., Martinez, O., Chua, M. A., Xiao, S., Cros, J. F., Martinez-Sobrido, L., Woo, S. L.C., Garcia-Sastre, A. (2007). Use of Reverse Genetics to Enhance the Oncolytic Properties of Newcastle Disease Virus. Cancer Res. 67: 8285-8292 [Abstract] [Full Text]  
• Hu, J., Sealfon, S. C., Hayot, F., Jayaprakash, C., Kumar, M., Pendleton, A. C., Ganee, A., Fernandez-Sesma, A., Moran, T. M., Wetmur, J. G. (2007). Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells. Nucleic Acids Res 0: gkm557v1-10 [Abstract] [Full Text]  
• DiNapoli, J. M., Kotelkin, A., Yang, L., Elankumaran, S., Murphy, B. R., Samal, S. K., Collins, P. L., Bukreyev, A. (2007). Newcastle disease virus, a host range-restricted virus, as a vaccine vector for intranasal immunization against emerging pathogens. Proc. Natl. Acad. Sci. USA 104: 9788-9793 [Abstract] [Full Text]  
• Hayman, A., Comely, S., Lackenby, A., Hartgroves, L. C. S., Goodbourn, S., McCauley, J. W., Barclay, W. S. (2007). NS1 Proteins of Avian Influenza A Viruses Can Act as Antagonists of the Human Alpha/Beta Interferon Response. J. Virol. 81: 2318-2327 [Abstract] [Full Text]  
• Li, Z., Jiang, Y., Jiao, P., Wang, A., Zhao, F., Tian, G., Wang, X., Yu, K., Bu, Z., Chen, H. (2006). The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. J. Virol. 80: 11115-11123 [Abstract] [Full Text]  
• Lichty, B. D., McBride, H., Hanson, S., Bell, J. C. (2006). Matrix protein of Vesicular stomatitis virus harbours a cryptic mitochondrial-targeting motif.. J. Gen. Virol. 87: 3379-3384 [Abstract] [Full Text]  
• Martinez-Sobrido, L., Zuniga, E. I., Rosario, D., Garcia-Sastre, A., de la Torre, J. C. (2006). Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus.. J. Virol. 80: 9192-9199 [Abstract] [Full Text]  
• Nanda, S. K., Baron, M. D. (2006). Rinderpest Virus Blocks Type I and Type II Interferon Action: Role of Structural and Nonstructural Proteins.. J. Virol. 80: 7555-7568 [Abstract] [Full Text]  
• Fernandez-Sesma, A., Marukian, S., Ebersole, B. J., Kaminski, D., Park, M.-S., Yuen, T., Sealfon, S. C., Garcia-Sastre, A., Moran, T. M. (2006). Influenza Virus Evades Innate and Adaptive Immunity via the NS1 Protein.. J. Virol. 80: 6295-6304 [Abstract] [Full Text]  
• Krishnamurthy, S., Takimoto, T., Scroggs, R. A., Portner, A. (2006). Differentially regulated interferon response determines the outcome of newcastle disease virus infection in normal and tumor cell lines.. J. Virol. 80: 5145-5155 [Abstract] [Full Text]  
• Cruz, C. D., Palosaari, H., Parisien, J.-P., Devaux, P., Cattaneo, R., Ouchi, T., Horvath, C. M. (2006). Measles Virus V Protein Inhibits p53 Family Member p73.. J. Virol. 80: 5644-5650 [Abstract] [Full Text]  
• Martinez-Sobrido, L., Gitiban, N., Fernandez-Sesma, A., Cros, J., Mertz, S. E., Jewell, N. A., Hammond, S., Flano, E., Durbin, R. K., Garcia-Sastre, A., Durbin, J. E. (2006). Protection against Respiratory Syncytial Virus by a Recombinant Newcastle Disease Virus Vector. J. Virol. 80: 1130-1139 [Abstract] [Full Text]  
• Nishio, M., Tsurudome, M., Ito, M., Ito, Y. (2005). Human Parainfluenza Virus Type 4 Is Incapable of Evading the Interferon-Induced Antiviral Effect. J. Virol. 79: 14756-14768 [Abstract] [Full Text]  
• Quinlivan, M., Zamarin, D., Garcia-Sastre, A., Cullinane, A., Chambers, T., Palese, P. (2005). Attenuation of Equine Influenza Viruses through Truncations of the NS1 Protein. J. Virol. 79: 8431-8439 [Abstract] [Full Text]  
• Nishio, M., Tsurudome, M., Ito, M., Garcin, D., Kolakofsky, D., Ito, Y. (2005). Identification of Paramyxovirus V Protein Residues Essential for STAT Protein Degradation and Promotion of Virus Replication. J. Virol. 79: 8591-8601 [Abstract] [Full Text]  
• Solorzano, A., Webby, R. J., Lager, K. M., Janke, B. H., Garcia-Sastre, A., Richt, J. A. (2005). Mutations in the NS1 Protein of Swine Influenza Virus Impair Anti-Interferon Activity and Confer Attenuation in Pigs. J. Virol. 79: 7535-7543 [Abstract] [Full Text]  
• Takeuchi, K., Takeda, M., Miyajima, N., Ami, Y., Nagata, N., Suzaki, Y., Shahnewaz, J., Kadota, S.-i., Nagata, K. (2005). Stringent Requirement for the C Protein of Wild-Type Measles Virus for Growth both In Vitro and in Macaques. J. Virol. 79: 7838-7844 [Abstract] [Full Text]  
• Donelan, N. R., Dauber, B., Wang, X., Basler, C. F., Wolff, T., Garcia-Sastre, A. (2004). The N- and C-Terminal Domains of the NS1 Protein of Influenza B Virus Can Independently Inhibit IRF-3 and Beta Interferon Promoter Activation. J. Virol. 78: 11574-11582 [Abstract] [Full Text]  
• Chatziandreou, N., Stock, N., Young, D., Andrejeva, J., Hagmaier, K., McGeoch, D. J., Randall, R. E. (2004). Relationships and host range of human, canine, simian and porcine isolates of simian virus 5 (parainfluenza virus 5). J. Gen. Virol. 85: 3007-3016 [Abstract] [Full Text]  
• Nakaya, Y., Nakaya, T., Park, M.-S., Cros, J., Imanishi, J., Palese, P., Garcia-Sastre, A. (2004). Induction of Cellular Immune Responses to Simian Immunodeficiency Virus Gag by Two Recombinant Negative-Strand RNA Virus Vectors. J. Virol. 78: 9366-9375 [Abstract] [Full Text]  
• Shaw, M. L., Garcia-Sastre, A., Palese, P., Basler, C. F. (2004). Nipah Virus V and W Proteins Have a Common STAT1-Binding Domain yet Inhibit STAT1 Activation from the Cytoplasmic and Nuclear Compartments, Respectively. J. Virol. 78: 5633-5641 [Abstract] [Full Text]  
• Sun, M., Rothermel, T. A., Shuman, L., Aligo, J. A., Xu, S., Lin, Y., Lamb, R. A., He, B. (2004). Conserved Cysteine-Rich Domain of Paramyxovirus Simian Virus 5 V Protein Plays an Important Role in Blocking Apoptosis. J. Virol. 78: 5068-5078 [Abstract] [Full Text]  
• Donelan, N. R., Basler, C. F., Garcia-Sastre, A. (2003). A Recombinant Influenza A Virus Expressing an RNA-Binding-Defective NS1 Protein Induces High Levels of Beta Interferon and Is Attenuated in Mice. J. Virol. 77: 13257-13266 [Abstract] [Full Text]  
• Munoz-Jordan, J. L., Sanchez-Burgos, G. G., Laurent-Rolle, M., Garcia-Sastre, A. (2003). Inhibition of interferon signaling by dengue virus. Proc. Natl. Acad. Sci. USA 100: 14333-14338 [Abstract] [Full Text]