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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Pham, Q. N.
Right arrow Articles by Buchholz, U. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pham, Q. N.
Right arrow Articles by Buchholz, U. J.

 Previous Article  |  Next Article 

Journal of Virology, December 2005, p. 15114-15122, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15114-15122.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Chimeric Recombinant Human Metapneumoviruses with the Nucleoprotein or Phosphoprotein Open Reading Frame Replaced by That of Avian Metapneumovirus Exhibit Improved Growth In Vitro and Attenuation In Vivo

Quynh N. Pham,{dagger} Stéphane Biacchesi,{dagger} Mario H. Skiadopoulos, Brian R. Murphy, Peter L. Collins, and Ursula J. Buchholz*

Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-8007

Received 21 July 2005/ Accepted 20 September 2005

Chimeric versions of recombinant human metapneumovirus (HMPV) were generated by replacing the nucleoprotein (N) or phosphoprotein (P) open reading frame with its counterpart from the closely related avian metapneumovirus (AMPV) subgroup C. In Vero cells, AMPV replicated to an approximately 100-fold-higher titer than HMPV. Surprisingly, the N and P chimeric viruses replicated to a peak titer that was 11- and 25-fold higher, respectively, than that of parental HMPV. The basis for this effect is not known but was not due to obvious changes in the efficiency of gene expression. AMPV and the N and P chimeras were evaluated for replication, immunogenicity, and protective efficacy in hamsters. AMPV was attenuated compared to HMPV in this mammalian host on day 5 postinfection, but not on day 3, and only in the nasal turbinates. In contrast, the N and P chimeras were reduced approximately 100-fold in both the upper and lower respiratory tract on day 3 postinfection, although there was little difference by day 5. The N and P chimeras induced a high level of neutralizing serum antibodies and protective efficacy against HMPV; AMPV was only weakly immunogenic and protective against HMPV challenge, reflecting antigenic differences. In African green monkeys immunized intranasally and intratracheally, the mean peak titer of the P chimera was reduced 100- and 1,000-fold in the upper and lower respiratory tracts, whereas the N chimera was reduced only 10-fold in the lower respiratory tract. Both chimeras were comparable to wild-type HMPV in immunogenicity and protective efficacy. Thus, the P chimera is a promising live HMPV vaccine candidate that paradoxically combines improved growth in vitro with attenuation in vivo.

* Corresponding author. Mailing address: Building 50, Room 6505, 50 South Dr., MSC 8007, Bethesda, MD 20892-8007. Phone: (301) 594-1533. Fax: (301) 496-8312. E-mail: ubuchholz{at}niaid.nih.gov.

{dagger} These authors contributed equally to the work.

Journal of Virology, December 2005, p. 15114-15122, Vol. 79, No. 24
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.24.15114-15122.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • de Graaf, M., Schrauwen, E. J. A., Herfst, S., van Amerongen, G., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2009). Fusion protein is the main determinant of metapneumovirus host tropism. J. Gen. Virol. 90: 1408-1416 [Abstract] [Full Text]  
  • de Graaf, M., Osterhaus, A. D. M. E., Fouchier, R. A. M., Holmes, E. C. (2008). Evolutionary dynamics of human and avian metapneumoviruses. J. Gen. Virol. 89: 2933-2942 [Abstract] [Full Text]  
  • Rout, S. N., Samal, S. K. (2008). The Large Polymerase Protein Is Associated with the Virulence of Newcastle Disease Virus. J. Virol. 82: 7828-7836 [Abstract] [Full Text]  
  • Herfst, S., de Graaf, M., Schrauwen, E. J. A., Sprong, L., Hussain, K., van den Hoogen, B. G., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2008). Generation of temperature-sensitive human metapneumovirus strains that provide protective immunity in hamsters. J. Gen. Virol. 89: 1553-1562 [Abstract] [Full Text]  
  • de Graaf, M., Herfst, S., Schrauwen, E. J. A., Choi, Y., van den Hoogen, B. G., Osterhaus, A. D. M. E., Fouchier, R. A. M. (2008). Specificity and functional interaction of the polymerase complex proteins of human and avian metapneumoviruses. J. Gen. Virol. 89: 975-983 [Abstract] [Full Text]  
  • Biacchesi, S., Murphy, B. R., Collins, P. L., Buchholz, U. J. (2007). Frequent Frameshift and Point Mutations in the SH Gene of Human Metapneumovirus Passaged In Vitro. J. Virol. 81: 6057-6067 [Abstract] [Full Text]  
  • Bukreyev, A., Skiadopoulos, M. H., Murphy, B. R., Collins, P. L. (2006). Nonsegmented Negative-Strand Viruses as Vaccine Vectors. J. Virol. 80: 10293-10306 [Full Text]  
  • Kahn, J. S. (2006). Epidemiology of Human Metapneumovirus. Clin. Microbiol. Rev. 19: 546-557 [Abstract] [Full Text]  
  • Govindarajan, D., Buchholz, U. J., Samal, S. K. (2006). Recovery of Avian Metapneumovirus Subgroup C from cDNA: Cross-Recognition of Avian and Human Metapneumovirus Support Proteins. J. Virol. 80: 5790-5797 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»