Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus
The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on...
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Published in | Japanese Journal of Infectious Diseases Vol. 69; no. 6; pp. 510 - 516 |
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Abstract | The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection. |
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AbstractList | The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection. The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection.The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV. In addition, human DPP4-expressing rat kidney fibroblasts, but not rat DPP4-expressing cells, were susceptible to MERS-CoV. Taken together, these results suggest that the rat is not a useful animal model for studying MERS-CoV infection. |
Author | Iwata-Yoshikawa, Naoko Suzuki, Tadaki Takeda, Makoto Fukuma, Aiko Fukushi, Shuetsu Nagata, Noriyo Hasegawa, Hideki Tashiro, Masato |
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Cites_doi | 10.1128/JVI.03427-14 10.1128/JVI.01967-06 10.1099/vir.0.060640-0 10.1016/j.vaccine.2011.02.085 10.1128/JVI.00983-14 10.1007/s00705-015-2506-z 10.1056/NEJMoa1211721 10.1128/CVI.00101-07 10.1128/JVI.00676-14 10.1371/journal.pone.0069127 10.1073/pnas.1310744110 10.1038/cr.2013.108 10.2147/IJGM.S67061 10.1073/pnas.1323279111 10.1016/0264-410X(91)90285-E 10.1038/nature12005 10.1371/journal.ppat.1004250 |
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References | 5. Coleman CM, Matthews KL, Goicochea L, et al. Wild type and innate immune deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J Gen Virol. 2014;95:408-12. 11. Saijo M, Georges-Courbot MC, Marianneau P, et al. Development of recombinant nucleoprotein-based diagnostic systems for Lassa fever. Clin Vaccine Immunol. 2007;14:1182-9. 15. van Doremalen N, Miazgowicz KL, Milne-Price S, et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol. 2014;88:9220-32. 6. Zhao J, Li K, Wohlford-Lenane C, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A. 2014;111:4970-5. 13. de Wit E, Rasmussen AL, Falzarano D, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A. 2013;110:16598-603. 9. Iwata-Yoshikawa N, Uda A, Suzuki T, et al. Effects of toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine. J Virol. 2014;88:8597-614. 17. Westdijk J, Brugmans D, Martin J, et al. Characterization and standardization of Sabin based inactivated polio vaccine: proposal for a new antigen unit for inactivated polio vaccines. Vaccine. 2011;29:3390-7. 1. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814-20. 2. Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495:251-4. 4. de Wit E, Prescott J, Baseler L, et al. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. PLoS One. 2013;8:e69127. 16. Anderson GW Jr, Lee JO, Anderson AO, et al. Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats. Vaccine. 1991;9:710-4. 8. Nagata N, Iwata N, Hasegawa H, et al. Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus. J Virol. 2007;81:1848-57. 10. Fukuma A, Tani H, Taniguchi S, et al. Inability of rat DPP4 to allow MERS-CoV infection revealed by using a VSV pseudotype bearing truncated MERS-CoV spike protein. Arch Virol. 2015;160:2293-300. 7. Agrawal AS, Garron T, Tao X, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol. 2015;89:3659-70. 14. Bosch BJ, Raj VS, Haagmans BL. Spiking the MERS-coronavirus receptor. Cell Res. 2013;23:1069-70. 12. Alghamdi IG, Hussain II, Almalki SS, et al. The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health. Int J Gen Med. 2014;7:417-23. 3. Falzarano D, de Wit E, Feldmann F, et al. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 2014;10:e1004250. 11 12 13 14 15 16 17 1 2 3 4 5 6 7 8 9 10 |
References_xml | – reference: 1. Zaki AM, van Boheemen S, Bestebroer TM, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012;367:1814-20. – reference: 4. de Wit E, Prescott J, Baseler L, et al. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. PLoS One. 2013;8:e69127. – reference: 7. Agrawal AS, Garron T, Tao X, et al. Generation of a transgenic mouse model of Middle East respiratory syndrome coronavirus infection and disease. J Virol. 2015;89:3659-70. – reference: 5. Coleman CM, Matthews KL, Goicochea L, et al. Wild type and innate immune deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J Gen Virol. 2014;95:408-12. – reference: 3. Falzarano D, de Wit E, Feldmann F, et al. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 2014;10:e1004250. – reference: 13. de Wit E, Rasmussen AL, Falzarano D, et al. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc Natl Acad Sci U S A. 2013;110:16598-603. – reference: 14. Bosch BJ, Raj VS, Haagmans BL. Spiking the MERS-coronavirus receptor. Cell Res. 2013;23:1069-70. – reference: 8. Nagata N, Iwata N, Hasegawa H, et al. Participation of both host and virus factors in induction of severe acute respiratory syndrome (SARS) in F344 rats infected with SARS coronavirus. J Virol. 2007;81:1848-57. – reference: 10. Fukuma A, Tani H, Taniguchi S, et al. Inability of rat DPP4 to allow MERS-CoV infection revealed by using a VSV pseudotype bearing truncated MERS-CoV spike protein. Arch Virol. 2015;160:2293-300. – reference: 17. Westdijk J, Brugmans D, Martin J, et al. Characterization and standardization of Sabin based inactivated polio vaccine: proposal for a new antigen unit for inactivated polio vaccines. Vaccine. 2011;29:3390-7. – reference: 16. Anderson GW Jr, Lee JO, Anderson AO, et al. Efficacy of a Rift Valley fever virus vaccine against an aerosol infection in rats. Vaccine. 1991;9:710-4. – reference: 15. van Doremalen N, Miazgowicz KL, Milne-Price S, et al. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J Virol. 2014;88:9220-32. – reference: 2. Raj VS, Mou H, Smits SL, et al. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495:251-4. – reference: 11. Saijo M, Georges-Courbot MC, Marianneau P, et al. Development of recombinant nucleoprotein-based diagnostic systems for Lassa fever. Clin Vaccine Immunol. 2007;14:1182-9. – reference: 6. Zhao J, Li K, Wohlford-Lenane C, et al. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc Natl Acad Sci U S A. 2014;111:4970-5. – reference: 12. Alghamdi IG, Hussain II, Almalki SS, et al. The pattern of Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive epidemiological analysis of data from the Saudi Ministry of Health. Int J Gen Med. 2014;7:417-23. – reference: 9. Iwata-Yoshikawa N, Uda A, Suzuki T, et al. Effects of toll-like receptor stimulation on eosinophilic infiltration in lungs of BALB/c mice immunized with UV-inactivated severe acute respiratory syndrome-related coronavirus vaccine. J Virol. 2014;88:8597-614. – ident: 7 doi: 10.1128/JVI.03427-14 – ident: 8 doi: 10.1128/JVI.01967-06 – ident: 5 doi: 10.1099/vir.0.060640-0 – ident: 17 doi: 10.1016/j.vaccine.2011.02.085 – ident: 9 doi: 10.1128/JVI.00983-14 – ident: 10 doi: 10.1007/s00705-015-2506-z – ident: 1 doi: 10.1056/NEJMoa1211721 – ident: 11 doi: 10.1128/CVI.00101-07 – ident: 15 doi: 10.1128/JVI.00676-14 – ident: 4 doi: 10.1371/journal.pone.0069127 – ident: 13 doi: 10.1073/pnas.1310744110 – ident: 14 doi: 10.1038/cr.2013.108 – ident: 12 doi: 10.2147/IJGM.S67061 – ident: 6 doi: 10.1073/pnas.1323279111 – ident: 16 doi: 10.1016/0264-410X(91)90285-E – ident: 2 doi: 10.1038/nature12005 – ident: 3 doi: 10.1371/journal.ppat.1004250 |
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SubjectTerms | Administration, Intranasal animal model Animals Cell Line Coronaviridae Disease Resistance Female Host Specificity Humans Immunohistochemistry Lung - virology MERS-CoV Middle East Respiratory Syndrome Coronavirus - growth & development Pregnancy rat Rats, Inbred F344 Rats, Inbred Lew susceptibility Viral Tropism |
Title | Non Susceptibility of Neonatal and Adult Rats against the Middle East Respiratory Syndrome Coronavirus |
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