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 Alymova, I. V.
Right arrow Articles by McCullers, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alymova, I. V.
Right arrow Articles by McCullers, J. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2005, p. 398-405, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.398-405.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Novel Parainfluenza Virus Hemagglutinin-Neuraminidase Inhibitor BCX 2798 Prevents Lethal Synergism between a Paramyxovirus and Streptococcus pneumoniae

Irina V. Alymova,1 Allen Portner,1 Toru Takimoto,1 Kelli L. Boyd,2 Y. Sudhakara Babu,3 and Jonathan A. McCullers1*

Department of Infectious Diseases,1 Animal Resources Center, St. Jude Children's Research Hospital, Memphis, Tennessee,2 BioCryst Pharmaceuticals, Inc., Birmingham, Alabama3

Received 12 April 2004/ Returned for modification 14 August 2004/ Accepted 22 September 2004

An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to prevent the synergism between a paramyxovirus and Streptococcus pneumoniae was examined in this study. A model of secondary bacterial pneumonia after infection with a recombinant Sendai virus whose hemagglutinin-neuraminidase gene was replaced with that of human parainfluenza virus type 1 [rSV(hHN)] was established in mice. Challenge of mice with a sublethal dose of S. pneumoniae 7 days after a sublethal infection with rSV(hHN) (synergistic group) caused 100% mortality. Bacterial infection preceding viral infection had no effect on survival. The mean bacterial titers in the synergistic group were significantly higher than in mice infected with bacteria only. The virus titers were similar in mice infected with rSV(hHN) alone and in dually infected mice. Intranasal administration of BCX 2798 at 10 mg/kg per day to the synergistic group of mice starting 4 h before virus infection protected 80% of animals from death. This effect was accompanied by a significant reduction in lung viral and bacterial titers. Treatment of mice 24 h after the rSV(hHN) infection showed no protection against synergistic lethality. Together, our results indicate that parainfluenza viruses can prime for secondary bacterial infections. Prophylaxis of parainfluenza virus infections with antivirals might be an effective strategy for prevention of secondary bacterial complications in humans.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794. Phone: (901) 495-5164. Fax: (901) 495-3099. E-mail: jon.mccullers{at}stjude.org.

Antimicrobial Agents and Chemotherapy, January 2005, p. 398-405, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.398-405.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Alymova, I. V., Taylor, G., Mishin, V. P., Watanabe, M., Murti, K. G., Boyd, K., Chand, P., Babu, Y. S., Portner, A. (2008). Loss of the N-Linked Glycan at Residue 173 of Human Parainfluenza Virus Type 1 Hemagglutinin-Neuraminidase Exposes a Second Receptor-Binding Site. J. Virol. 82: 8400-8410 [Abstract] [Full Text]  
  • McCullers, J. A. (2006). Insights into the Interaction between Influenza Virus and Pneumococcus. Clin. Microbiol. Rev. 19: 571-582 [Abstract] [Full Text]  
  • Avadhanula, V., Rodriguez, C. A., DeVincenzo, J. P., Wang, Y., Webby, R. J., Ulett, G. C., Adderson, E. E. (2006). Respiratory Viruses Augment the Adhesion of Bacterial Pathogens to Respiratory Epithelium in a Viral Species- and Cell Type-Dependent Manner. J. Virol. 80: 1629-1636 [Abstract] [Full Text]  
  • Porotto, M., Fornabaio, M., Greengard, O., Murrell, M. T., Kellogg, G. E., Moscona, A. (2006). Paramyxovirus Receptor-Binding Molecules: Engagement of One Site on the Hemagglutinin-Neuraminidase Protein Modulates Activity at the Second Site. J. Virol. 80: 1204-1213 [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»