This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bartlett, E. J.
Right arrow Articles by Pickles, R. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bartlett, E. J.
Right arrow Articles by Pickles, R. J.

 Previous Article  |  Next Article 

Journal of Virology, August 2008, p. 8059-8070, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.02263-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Role of Interferon in the Replication of Human Parainfluenza Virus Type 1 Wild Type and Mutant Viruses in Human Ciliated Airway Epithelium{triangledown}

Emmalene J. Bartlett,1,{dagger} Margaret Hennessey,2,3,{dagger} Mario H. Skiadopoulos,1 Alexander C. Schmidt,1 Peter L. Collins,1 Brian R. Murphy,1 and Raymond J. Pickles2,3*

Laboratory of Infectious Diseases, Respiratory Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892-2007,1 Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7248,2 Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-72483

Received 18 October 2007/ Accepted 29 May 2008

Human parainfluenza virus type 1 (HPIV1) is a significant cause of pediatric respiratory disease in the upper and lower airways. An in vitro model of human ciliated airway epithelium (HAE), a useful tool for studying respiratory virus-host interactions, was used in this study to show that HPIV1 selectively infects ciliated cells within the HAE and that progeny virus is released from the apical surface with little apparent gross cytopathology. In HAE, type I interferon (IFN) is induced following infection with an HPIV1 mutant expressing defective C proteins with an F170S amino acid substitution, rHPIV1-CF170S, but not following infection with wild-type HPIV1. IFN induction coincided with a 100- to 1,000-fold reduction in virus titer, supporting the hypothesis that the HPIV1 C proteins are critical for the inhibition of the innate immune response. Two recently characterized live attenuated HPIV1 vaccine candidates expressing mutant C proteins were also evaluated in HAE. The vaccine candidates, rHPIV1-CR84G/{Delta}170HNT553ALY942A and rHPIV1-CR84G/{Delta}170HNT553AL{Delta}1710-11, which contain temperature-sensitive (ts) attenuating (att) and non-ts att mutations, were highly restricted in growth in HAE at permissive (32°C) and restrictive (37°C) temperatures. The viruses grew slightly better at 37°C than at 32°C, and rHPIV1-CR84G/{Delta}170HNT553ALY942A was less attenuated than rHPIV1-CR84G/{Delta}170HNT553AL{Delta}1710-11. The level of replication in HAE correlated with that previously observed for African green monkeys, suggesting that the HAE model has potential as a tool for the preclinical evaluation of HPIV1 vaccines, although how these in vitro data will correlate with vaccine virus replication in seronegative human subjects remains to be seen.

* Corresponding author. Mailing address: Cystic Fibrosis/Pulmonary Research and Treatment Center, UNC School of Medicine, 7023 Thurston-Bowles, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7248. Phone: (919) 966-7044. Fax: (919) 966-5178. E-mail: branston{at}med.unc.edu

{triangledown} Published ahead of print on 4 June 2008.

{dagger} E.J.B. and M.H. contributed equally to this study.

Journal of Virology, August 2008, p. 8059-8070, Vol. 82, No. 16
0022-538X/08/$08.00+0     doi:10.1128/JVI.02263-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chambers, R., Takimoto, T. (2009). Host specificity of the anti-interferon and anti-apoptosis activities of parainfluenza virus P/C gene products. J. Gen. Virol. 90: 1906-1915 [Abstract] [Full Text]  
  • Boonyaratanakornkit, J. B., Bartlett, E. J., Amaro-Carambot, E., Collins, P. L., Murphy, B. R., Schmidt, A. C. (2009). The C Proteins of Human Parainfluenza Virus Type 1 (HPIV1) Control the Transcription of a Broad Array of Cellular Genes That Would Otherwise Respond to HPIV1 Infection. J. Virol. 83: 1892-1910 [Abstract] [Full Text]  
  • Donaldson, E. F., Yount, B., Sims, A. C., Burkett, S., Pickles, R. J., Baric, R. S. (2008). Systematic Assembly of a Full-Length Infectious Clone of Human Coronavirus NL63. J. Virol. 82: 11948-11957 [Abstract] [Full Text]  
  • Bartlett, E. J., Cruz, A.-M., Esker, J., Castano, A., Schomacker, H., Surman, S. R., Hennessey, M., Boonyaratanakornkit, J., Pickles, R. J., Collins, P. L., Murphy, B. R., Schmidt, A. C. (2008). Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates. J. Virol. 82: 8965-8977 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»