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 inJapanese Journal of Infectious Diseases Vol. 69; no. 6; pp. 510 - 516
Main Authors Iwata-Yoshikawa, Naoko, Fukushi, Shuetsu, Fukuma, Aiko, Suzuki, Tadaki, Takeda, Makoto, Tashiro, Masato, Hasegawa, Hideki, Nagata, Noriyo
Format Journal Article
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Published Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 2016
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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.
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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  fullname: Iwata-Yoshikawa, Naoko
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  fullname: Suzuki, Tadaki
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  fullname: Takeda, Makoto
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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.
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Snippet The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a...
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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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