1887

Abstract

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.060640-0
2014-02-01
2019-09-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/95/2/408.html?itemId=/content/journal/jgv/10.1099/vir.0.060640-0&mimeType=html&fmt=ahah

References

  1. Chan J. F., Chan K. H., Choi G. K., To K. K., Tse H., Cai J. P., Yeung M. L., Cheng V. C., Chen H.. & other authors ( 2013; ). Differential cell line susceptibility to the emerging novel human betacoronavirus 2c EMC/2012: implications for disease pathogenesis and clinical manifestation. . J Infect Dis 207:, 1743–1752. [CrossRef] [PubMed]
    [Google Scholar]
  2. Corman V. M., Eckerle I., Bleicker T., Zaki A., Landt O., Eschbach-Bludau M., van Boheemen S., Gopal R., Ballhause M.. & other authors ( 2012a; ). Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. . Eurosurveillance 17:, 39.[PubMed]
    [Google Scholar]
  3. Corman V. M., Muller M. A., Costabel U., Timm J., Binger T., Meyer B., Kreher P., Lattwein E., Eschbach-Bludau M.. & other authors ( 2012b; ). Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. . Eurosurveillance 17, 49.
    [Google Scholar]
  4. de Wit E., Prescott J., Baseler L., Bushmaker T., Thomas T., Lackemeyer M. G., Martellaro C., Milne-Price S., Haddock E.. & other authors ( 2013; ). The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. . PLoS ONE 8:, e69127. [CrossRef] [PubMed]
    [Google Scholar]
  5. Drosten C., Seilmaier M., Corman V. M., Hartmann W., Scheible G., Sack S., Guggemos W., Kallies R., Muth D.. & other authors ( 2013; ). Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. . Lancet Infect Dis 13:, 745–751. [CrossRef] [PubMed]
    [Google Scholar]
  6. Frieman M. B., Chen J., Morrison T. E., Whitmore A., Funkhouser W., Ward J. M., Lamirande E. W., Roberts A., Heise M.. & other authors ( 2010; ). SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism. . PLoS Pathog 6:, e1000849. [CrossRef] [PubMed]
    [Google Scholar]
  7. Kindler E., Jónsdóttir H. R., Muth D., Hamming O. J., Hartmann R., Rodriguez R., Geffers R., Fouchier R. A., Drosten C.. & other authors ( 2013; ). Efficient replication of the novel human betacoronavirus EMC on primary human epithelium highlights its zoo-notic potential. . mBio 4:, e00611–e00612. [CrossRef] [PubMed]
    [Google Scholar]
  8. Mailles A., Blanckaert K., Chaud P., van der Werf S., Lina B., Caro V., Campese C., Guéry B., Prouvost H.. & other authors ( 2013; ). First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013. . Eurosurveillance 18:, 24.[PubMed]
    [Google Scholar]
  9. Memish Z. A., Zumla A. I., Al-Hakeem R. F., Al-Rabeeah A. A., Stephens G. M.. ( 2013; ). Family cluster of Middle East respiratory syndrome coronavirus infections. . N Engl J Med 368:, 2487–2494. [CrossRef] [PubMed]
    [Google Scholar]
  10. Müller M. A., Raj V. S., Muth D., Meyer B., Kallies S., Smits S. L., Wollny R., Bestebroer T. M., Specht S.. & other authors ( 2012; ). Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. . MBio 3:, e00515-12. [CrossRef] [PubMed]
    [Google Scholar]
  11. Munster V. J., de Wit E., Feldmann H.. ( 2013; ). Pneumonia from human coronavirus in a macaque model. . N Engl J Med 368:, 1560–1562. [CrossRef] [PubMed]
    [Google Scholar]
  12. Perera R., Wang P., Gomaa M., El-Shesheny R., Kandeil A., Bagato O., Siu L., Shehata M., Kayed A.. & other authors ( 2013; ). Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in dromedary camels in Egypt, June 2013. . Eurosurveillance 18:, 18. [CrossRef] [PubMed]
    [Google Scholar]
  13. Raj V. S., Mou H., Smits S. L., Dekkers D. H., Müller M. A., Dijkman R., Muth D., Demmers J. A., Zaki A.. & other authors ( 2013; ). Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. . Nature 495:, 251–254. [CrossRef] [PubMed]
    [Google Scholar]
  14. Reed L. J., Muench H.. ( 1938; ). A simple method of estimating fifty per cent endpoints. . Am J Epidemiol 27:, 493–497.
    [Google Scholar]
  15. Reusken C. B., Haagmans B. L., Müller M. A., Gutierrez C., Godeke G. J., Meyer B., Muth D., Raj V. S., Vries L. S.. & other authors ( 2013; ). Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. . Lancet Infect Dis 13:, 859–866. [CrossRef] [PubMed]
    [Google Scholar]
  16. Roberts A., Deming D., Paddock C. D., Cheng A., Yount B., Vogel L., Herman B. D., Sheahan T., Heise M.. & other authors ( 2007; ). A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. . PLoS Pathog 3:, e5. [CrossRef] [PubMed]
    [Google Scholar]
  17. Sheahan T., Morrison T. E., Funkhouser W., Uematsu S., Akira S., Baric R. S., Heise M. T.. ( 2008; ). MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV. . PLoS Pathog 4:, e1000240. [CrossRef] [PubMed]
    [Google Scholar]
  18. van Boheemen S., de Graaf M., Lauber C., Bestebroer T. M., Raj V. S., Zaki A. M., Osterhaus A. D., Haagmans B. L., Gorbalenya A. E.. & other authors ( 2012; ). Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. . MBio 3:, e00473-12. [CrossRef] [PubMed]
    [Google Scholar]
  19. Zielecki F., Weber M., Eickmann M., Spiegelberg L., Zaki A. M., Matrosovich M., Becker S., Weber F.. ( 2013; ). Human cell tropism and innate immune system interactions of human respiratory coronavirus EMC compared to those of severe acute respiratory syndrome coronavirus. . J Virol 87:, 5300–5304. [CrossRef] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.060640-0
Loading
/content/journal/jgv/10.1099/vir.0.060640-0
Loading

Data & Media loading...

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error