This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow A correction has been published
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 Biacchesi, S.
Right arrow Articles by Buchholz, U. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Biacchesi, S.
Right arrow Articles by Buchholz, U. J.

 Previous Article

Journal of Virology, October 2005, p. 12608-12613, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12608-12613.2005

Infection of Nonhuman Primates with Recombinant Human Metapneumovirus Lacking the SH, G, or M2-2 Protein Categorizes Each as a Nonessential Accessory Protein and Identifies Vaccine Candidates

Stéphane Biacchesi, Quynh N. Pham, 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 1 June 2005/ Accepted 5 July 2005

Recombinant human metapneumovirus (HMPV) in which the SH, G, or M2 gene or open reading frame was deleted by reverse genetics was evaluated for replication and vaccine efficacy following topical administration to the respiratory tract of African green monkeys, a permissive primate host. Replication of the {Delta}SH virus was only marginally less efficient than that of wild-type HMPV, whereas the {Delta}G and {Delta}M2-2 viruses were reduced sixfold and 160-fold in the upper respiratory tract and 3,200-fold and 4,000-fold in the lower respiratory tract, respectively. Even with the highly attenuated mutants, there was unequivocal HMPV replication at each anatomical site in each animal. Thus, none of these three proteins is essential for HMPV replication in a primate host, although G and M2-2 increased the efficiency of replication. Each gene-deletion virus was highly immunogenic and protective against wild-type HMPV challenge. The {Delta}G and {Delta}M2-2 viruses are promising vaccine candidates that are based on independent mechanisms of attenuation and are appropriate for clinical evaluation.

* Corresponding author. Mailing address: National Institutes of Health, NIAID, 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.

Journal of Virology, October 2005, p. 12608-12613, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12608-12613.2005




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]  
  • Thammawat, S., Sadlon, T. A., Hallsworth, P. G., Gordon, D. L. (2008). Role of Cellular Glycosaminoglycans and Charged Regions of Viral G Protein in Human Metapneumovirus Infection. J. Virol. 82: 11767-11774 [Abstract] [Full Text]  
  • Mok, H., Tollefson, S. J., Podsiad, A. B., Shepherd, B. E., Polosukhin, V. V., Johnston, R. E., Williams, J. V., Crowe, J. E. Jr (2008). An Alphavirus Replicon-Based Human Metapneumovirus Vaccine Is Immunogenic and Protective in Mice and Cotton Rats. J. Virol. 82: 11410-11418 [Abstract] [Full Text]  
  • Bao, X., Kolli, D., Liu, T., Shan, Y., Garofalo, R. P., Casola, A. (2008). Human Metapneumovirus Small Hydrophobic Protein Inhibits NF-{kappa}B Transcriptional Activity. J. Virol. 82: 8224-8229 [Abstract] [Full Text]  
  • Endo, R., Ebihara, T., Ishiguro, N., Teramoto, S., Ariga, T., Sakata, C., Hayashi, A., Ishiko, H., Kikuta, H. (2008). Detection of four genetic subgroup-specific antibodies to human metapneumovirus attachment (G) protein in human serum. J. Gen. Virol. 89: 1970-1977 [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]  
  • Ling, R., Sinkovic, S., Toquin, D., Guionie, O., Eterradossi, N., Easton, A. J. (2008). Deletion of the SH gene from avian metapneumovirus has a greater impact on virus production and immunogenicity in turkeys than deletion of the G gene or M2-2 open reading frame. J. Gen. Virol. 89: 525-533 [Abstract] [Full Text]  
  • Liu, L., Bastien, N., Li, Y. (2007). Intracellular Processing, Glycosylation, and Cell Surface Expression of Human Metapneumovirus Attachment Glycoprotein. J. Virol. 81: 13435-13443 [Abstract] [Full Text]  
  • Hamelin, M.-E., Couture, C., Sackett, M. K., Boivin, G. (2007). Enhanced lung disease and Th2 response following human metapneumovirus infection in mice immunized with the inactivated virus. J. Gen. Virol. 88: 3391-3400 [Abstract] [Full Text]  
  • Krempl, C. D., Wnekowicz, A., Lamirande, E. W., Nayebagha, G., Collins, P. L., Buchholz, U. J. (2007). Identification of a Novel Virulence Factor in Recombinant Pneumonia Virus of Mice. J. Virol. 81: 9490-9501 [Abstract] [Full Text]  
  • Naylor, C. J., Ling, R., Edworthy, N., Savage, C. E., Easton, A. J. (2007). Avian metapneumovirus SH gene end and G protein mutations influence the level of protection of live-vaccine candidates. J. Gen. Virol. 88: 1767-1775 [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]  
  • van den Hoogen, B. G., Herfst, S., de Graaf, M., Sprong, L., van Lavieren, R., van Amerongen, G., Yuksel, S., Fouchier, R. A. M., Osterhaus, A. D. M. E., de Swart, R. L. (2007). Experimental infection of macaques with human metapneumovirus induces transient protective immunity. J. Gen. Virol. 88: 1251-1259 [Abstract] [Full Text]  
  • Schowalter, R. M., Smith, S. E., Dutch, R. E. (2006). Characterization of Human Metapneumovirus F Protein-Promoted Membrane Fusion: Critical Roles for Proteolytic Processing and Low pH. J. Virol. 80: 10931-10941 [Abstract] [Full Text]  
  • Kahn, J. S. (2006). Epidemiology of Human Metapneumovirus. Clin. Microbiol. Rev. 19: 546-557 [Abstract] [Full Text]  
  • Biacchesi, S., Pham, Q. N., Skiadopoulos, M. H., Murphy, B. R., Collins, P. L., Buchholz, U. J. (2006). Modification of the Trypsin-Dependent Cleavage Activation Site of the Human Metapneumovirus Fusion Protein To Be Trypsin Independent Does Not Increase Replication or Spread in Rodents or Nonhuman Primates.. J. Virol. 80: 5798-5806 [Abstract] [Full Text]  
  • Pham, Q. N., Biacchesi, S., Skiadopoulos, M. H., Murphy, B. R., Collins, P. L., Buchholz, U. J. (2005). 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. J. Virol. 79: 15114-15122 [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»