Development of animal models against emerging coronaviruses: From SARS to MERS coronavirus

Troy C Sutton, Kanta Subbarao, Troy C Sutton, Kanta Subbarao

Abstract

Two novel coronaviruses have emerged to cause severe disease in humans. While bats may be the primary reservoir for both viruses, SARS coronavirus (SARS-CoV) likely crossed into humans from civets in China, and MERS coronavirus (MERS-CoV) has been transmitted from camels in the Middle East. Unlike SARS-CoV that resolved within a year, continued introductions of MERS-CoV present an on-going public health threat. Animal models are needed to evaluate countermeasures against emerging viruses. With SARS-CoV, several animal species were permissive to infection. In contrast, most laboratory animals are refractory or only semi-permissive to infection with MERS-CoV. This host-range restriction is largely determined by sequence heterogeneity in the MERS-CoV receptor. We describe animal models developed to study coronaviruses, with a focus on host-range restriction at the level of the viral receptor and discuss approaches to consider in developing a model to evaluate countermeasures against MERS-CoV.

Keywords: Animal models; Coronaviruses; MERS-CoV; Receptor; SARS-CoV.

Copyright © 2015. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Schematic of strategies to develop an animal model to meet the FDA Animal Efficacy Rule. Under the FDA׳s Animal Efficacy Rule (“Animal Rule”) therapeutics against rare, emerging, or virulent agents can achieve regulatory approval provided efficacy is demonstrated in two animal models (one of which must be a non-rodent species). Animal species of interest must first be evaluated for permissiveness to viral replication and presentation of clinical disease. As an alternative, in animal species that are permissive but do not show clinical disease, serial passage can be performed. After an animal model has been developed the resulting disease must be characterized. The ideal animal model is permissive to infection and reproduces the clinical illness and pathology observed in humans.

References

    1. Adney R.R., van Doremalen N., VBrown V.R., Bushmater T., Scott D., de Wit E. Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels. Emerg. Infect. Dis. 2014;20(12):1999–2005.
    1. Al-Tawfiq J.A., Memish Z.A. Middle East respiratory syndrome coronavirus: epidemiology and disease control measures. Infect. Drug Resist. 2014;7:281–287.
    1. Alagaili A.N., Briese T., Mishra N., Kapoor V., Sameroff S.C., Burbelo P.D. Middle East respiratory syndrome coronavirus infection in dromedary camels in Saudi Arabia. mBio. 2014;5(2):e00884-14.
    1. Azhar E.I., El-Kafrawy S.A., Farraj S.A., Hassan A.M., Al-Saeed M.S., Hashem A.M. Evidence for camel-to-human transmission of MERS coronavirus. N. Engl. J. Med. 2014;370(26):2499–2505.
    1. Barlan A., Zhao J., Sarkar M.K., Li K., McCray P.B., Jr., Perlman S. Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection. J. Virol. 2014;88(9):4953–4961.
    1. Bermingham A., Chand M.A., Brown C.S., Aarons E., Tong C., Langrish C. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Eurosurveillance. 2012;17(40):20290.
    1. Bisht H., Roberts A., Vogel L., Bukreyev A., Collins P.L., Murphy B.R. Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice. Proc. Natl. Acad. Sci. USA. 2004;101(17):6641–6646.
    1. Booth C.M., Matukas L.M., Tomlinson G.A., Rachlis A.R., Rose D.B., Dwosh H.A. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. J. Am. Med. Assoc. 2003;289(21):2801–2809.
    1. Buchholz U.J., Bukreyev A., Yang L., Lamirande E.W., Murphy B.R., Subbarao K. Contributions of the structural proteins of severe acute respiratory syndrome coronavirus to protective immunity. Proc. Natl. Acad. Sci. USA. 2004;101(26):9804–9809.
    1. Chan J.F., Chan K.H., Kao R.Y., To K.K., Zheng B.J., Li C.P. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J. Infect. 2013;67(6):606–616.
    1. Chan J.W., Ng C.K., Chan Y.H., Mok T.Y., Lee S., Chu S.Y. Short term outcome and risk factors for adverse clinical outcomes in adults with severe acute respiratory syndrome (SARS) Thorax. 2003;58(8):686–689.
    1. Chinese SMEC Molecular evolution of the SARS coronavirus during the course of the SARS epidemic in China. Science. 2004;303(5664):1666–1669.
    1. Chu Y.K., Ali G.D., Jia F., Li Q., Kelvin D., Couch R.C. The SARS-CoV ferret model in an infection-challenge study. Virology. 2008;374(1):151–163.
    1. Cockrell A.S., Peck K.M., Yount B.L., Agnihothram S.S., Scobey T., Curnes N.R. Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection. J. Virol. 2014;88(9):5195–5199.
    1. Coleman C.M., Matthews K.L., Goicochea L., Frieman M.B. Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus. J. Gen. Virol. 2014;95(Pt 2):408–412.
    1. Coleman C.M., Liu Y.V., Mu H., Taylor J.K., Massare M., Flyer D.C. Purified coronavirus spike protein nanoparticles induce coronavirus neutralizing antibodies in mice. Vaccine. 2014;32(26):3169–3174.
    1. Darnell M.E., Plant E.P., Watanabe H., Byrum R., St, Claire M., Ward J.M. Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets. J. Infect. Dis. 2007;196(9):1329–1338.
    1. Day C.W., Baric R., Cai S.X., Frieman M., Kumaki Y., Morrey J.D. A new mouse-adapted strain of SARS-CoV as a lethal model for evaluating antiviral agents in vitro and in vivo. Virology. 2009;395(2):210–222.
    1. de Wilde A.H., Jochmans D., Posthuma C.C., Zevenhoven-Dobbe J.C., van Nieuwkoop S., Bestebroer T.M. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob. Agents Chemother. 2014;58(8):4875–4884.
    1. de Wit E., Rasmussen A.L., Falzarano D., Bushmaker T., Feldmann F., Brining D.L. Middle East respiratory syndrome coronavirus (MERS-CoV) causes transient lower respiratory tract infection in rhesus macaques. Proc. Natl. Acad. Sci. USA. 2013;110(41):16598–16603.
    1. de Wit E., Prescott J., Baseler L., Bushmaker T., Thomas T., Lackemeyer M.G. The Middle East respiratory syndrome coronavirus (MERS-CoV) does not replicate in Syrian hamsters. PloS One. 2013;8(7):e69127.
    1. Ding Y., Wang H., Shen H., Li Z., Geng J., Han H. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J. Pathol. 2003;200(3):282–289.
    1. Donnelly C.A., Ghani A.C., Leung G.M., Hedley A.J., Fraser C., Riley S. Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong. Lancet. 2003;361(9371):1761–1766.
    1. Doudna J.A., Charpentier E. Genome editing. the new frontier of genome engineering with CRISPR–Cas9. Science. 2014;346(6213):1258096.
    1. Dyall J., Coleman C.M., Hart B.J., Venkataraman T., Holbrook M.R., Kindrachuk J. Repurposing of clinically developed drugs for treatment of Middle East respiratory syndrome coronavirus infection. Antimicrob. Agents Chemother. 2014;58(8):4885–4893.
    1. ECDC, 2014. Communicable Disease Threats Report Week 50, European Centre for Disease Prevention and Control, Sweden [cited 2014 December 14, 2014]. Available from: .
    1. FDA, 2014. Guidance for industry product development under the animal rule. In: US Department of Health and Human Services (May 2014 ed.), Food and Drug Administration (FDA); Silver Spring, MD
    1. Falzarano D., de Wit E., Rasmussen A.L., Feldmann F., Okumura A., Scott D.P. Treatment with interferon-alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat. Med. 2013;19(10):1313–1317.
    1. Falzarano D., de Wit E., Feldmann F., Rasmussen A.L., Okumura A., Peng X. Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog. 2014;10(8):e1004250.
    1. Fouchier R.A., Kuiken T., Schutten M., van Amerongen G., van Doornum G.J., van den Hoogen B.G. Aetiology: Koch׳s postulates fulfilled for SARS virus. Nature. 2003;423(6937):240.
    1. Franks T.J., Chong P.Y., Chui P., Galvin J.R., Lourens R.M., Reid A.H. Lung pathology of severe acute respiratory syndrome (SARS): a study of 8 autopsy cases from Singapore. Hum. Pathol. 2003;34(8):743–748.
    1. Frieman M., Yount B., Agnihothram S., Page C., Donaldson E., Roberts A. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease. J. Virol. 2012;86(2):884–897.
    1. Frieman M.B., Chen J., Morrison T.E., Whitmore A., Funkhouser W., Ward J.M. SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism. PLoS Pathog. 2010;6(4):e1000849.
    1. Ge X.Y., Li J.L., Yang X.L., Chmura A.A., Zhu G., Epstein J.H. Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor. Nature. 2013;503(7477):535–538.
    1. Glass W.G., Subbarao K., Murphy B., Murphy P.M. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J. Immunol. 2004;173(6):4030–4039.
    1. Graham R.L., Donaldson E.F., Baric R.S. A decade after SARS: strategies for controlling emerging coronaviruses. Nat. Rev. Microbiol. 2013;11(12):836–848.
    1. Greenough T.C., Carville A., Coderre J., Somasundaran M., Sullivan J.L., Luzuriaga K. Pneumonitis and multi-organ system disease in common marmosets (Callithrix jacchus) infected with the severe acute respiratory syndrome-associated coronavirus. Am. J. Pathol. 2005;167(2):455–463.
    1. Haagmans B.L., Al Dhahiry S.H., Reusken C.B., Raj V.S., Galiano M., Myers R. Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation. Lancet Infect. Dis. 2014;14(2):140–145.
    1. Hart B.J., Dyall J., Postnikova E., Zhou H., Kindrachuk J., Johnson R.F. Interferon-beta and mycophenolic acid are potent inhibitors of Middle East respiratory syndrome coronavirus in cell-based assays. J. Gen. Virol. 2014;95(Pt 3):571–577.
    1. Hemida M.G., Perera R.A., Wang P., Alhammadi M.A., Siu L.Y., Li M. Middle East respiratory syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia, 2010 to 2013. Eurosurveillance. 2013;18(50):20659.
    1. Hilgenfeld R., Peiris M. From SARS to MERS: 10 years of research on highly pathogenic human coronaviruses. Antivir. Res. 2013;100(1):286–295.
    1. Hogan R.J., Gao G., Rowe T., Bell P., Flieder D., Paragas J. Resolution of primary severe acute respiratory syndrome-associated coronavirus infection requires Stat1. J. Virol. 2004;78(20):11416–11421.
    1. Jeffers S.A., Tusell S.M., Gillim-Ross L., Hemmila E.M., Achenbach J.E., Babcock G.J. CD209L (L-SIGN) is a receptor for severe acute respiratory syndrome coronavirus. Proc. Natl. Acad. Sci. USA. 2004;101(44):15748–15753.
    1. Karlberg J., Chong D.S., Lai W.Y. Do men have a higher case fatality rate of severe acute respiratory syndrome than women do? Am. J. Epidemiol. 2004;159(3):229–231.
    1. Kim E., Okada K., Kenniston T., Raj V.S., AlHajri M.M., Farag E.A. Immunogenicity of an adenoviral-based Middle East respiratory syndrome coronavirus vaccine in BALB/c mice. Vaccine. 2014;32(45):5975–5982.
    1. Kobinger G.P., Figueredo J.M., Rowe T., Zhi Y., Gao G., Sanmiguel J.C. Adenovirus-based vaccine prevents pneumonia in ferrets challenged with the SARS coronavirus and stimulates robust immune responses in macaques. Vaccine. 2007;25(28):5220–5231.
    1. Ksiazek T.G., Erdman D., Goldsmith C.S., Zaki S.R., Peret T., Emery S. A novel coronavirus associated with severe acute respiratory syndrome. N. Engl. J. Med. 2003;348(20):1953–1966.
    1. Kuiken T., Fouchier R.A., Schutten M., Rimmelzwaan G.F., van Amerongen G., van Riel D. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003;362(9380):263–270.
    1. Lamirande E.W., DeDiego M.L., Roberts A., Jackson J.P., Alvarez E., Sheahan T. A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in golden Syrian hamsters. J. Virol. 2008;82(15):7721–7724.
    1. Lau S.K., Woo P.C., Li K.S., Huang Y., Tsoi H.W., Wong B.H. Severe acute respiratory syndrome coronavirus-like virus in Chinese horseshoe bats. Proc. Natl. Acad. Sci. USA. 2005;102(39):14040–14045.
    1. Lawler J.V., Endy T.P., Hensley L.E., Garrison A., Fritz E.A., Lesar M. Cynomolgus macaque as an animal model for severe acute respiratory syndrome. PLoS Med. 2006;3(5):e149.
    1. Li F. Structural analysis of major species barriers between humans and palm civets for severe acute respiratory syndrome coronavirus infections. J. Virol. 2008;82(14):6984–6991.
    1. Li F., Li W., Farzan M., Harrison S.C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science. 2005;309(5742):1864–1868.
    1. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–454.
    1. Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M., Sullivan J.L. Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2. J. Virol. 2004;78(20):11429–11433.
    1. Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S. Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2. EMBO J. 2005;24(8):1634–1643.
    1. Liang G., Chen Q., Xu J., Liu Y., Lim W., Peiris J.S. Laboratory diagnosis of four recent sporadic cases of community-acquired SARS, Guangdong Province, China. Emerg. Infect. Dis. 2004;10(10):1774–1781.
    1. Liang L., He C., Lei M., Li S., Hao Y., Zhu H. Pathology of guinea pigs experimentally infected with a novel reovirus and coronavirus isolated from SARS patients. DNA Cell Biol. 2005;24(8):485–490.
    1. Lu G., Hu Y., Wang Q., Qi J., Gao F., Li Y. Molecular basis of binding between novel human coronavirus MERS-CoV and its receptor CD26. Nature. 2013;500(7461):227–231.
    1. Martina B.E., Haagmans B.L., Kuiken T., Fouchier R.A., Rimmelzwaan G.F., Van Amerongen G. Virology: SARS virus infection of cats and ferrets. Nature. 2003;425(6961):915.
    1. Masters P.S., Perlman S. Coronaviruses. In: Knipe D.M., Howley P.M., editors. Vol. 6. Lippincott Williams; Philadelphia: 2013. pp. 825–858. (Fields Virology).
    1. McAuliffe J., Vogel L., Roberts A., Fahle G., Fischer S., Shieh W.J. Replication of SARS coronavirus administered into the respiratory tract of African Green, rhesus and cynomolgus monkeys. Virology. 2004;330(1):8–15.
    1. McCray P.B., Jr., Pewe L., Wohlford-Lenane C., Hickey M., Manzel L., Shi L. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J. Virol. 2007;81(2):813–821.
    1. Memish Z.A., Cotten M., Meyer B., Watson S.J., Alsahafi A.J., Al Rabeeah A.A. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg. Infect. Dis. 2014;20(6):1012–1015.
    1. Meyer B., Muller M.A., Corman V.M., Reusken C.B., Ritz D., Godeke G.J. Antibodies against MERS coronavirus in dromedary camels, United Arab Emirates, 2003 and 2013. Emerg. Infect. Dis. 2014;20(4):552–559.
    1. Munster V.J., de Wit E., Feldmann H. Pneumonia from human coronavirus in a macaque model. N. Engl. J. Med. 2013;368(16):1560–1562.
    1. Netland J., Meyerholz D.K., Moore S., Cassell M., Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 2008;82(15):7264–7275.
    1. Nicholls J.M., Poon L.L., Lee K.C., Ng W.F., Lai S.T., Leung C.Y. Lung pathology of fatal severe acute respiratory syndrome. Lancet. 2003;361(9371):1773–1778.
    1. Normile D. Infectious diseases. Second lab accident fuels fears about SARS. Science. 2004;303(5654):26.
    1. Normile D., Vogel G. Infectious diseases. Early indications point to lab infection in new SARS case. Science. 2003;301(5640):1642–1643.
    1. Nowotny N., Kolodziejek J. Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels, Oman, 2013. Eurosurveillance. 2014;19(16):20781.
    1. Peiris J.S., Lai S.T., Poon L.L., Guan Y., Yam L.Y., Lim W. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet. 2003;361(9366):1319–1325.
    1. Poutanen S.M., Low D.E., Henry B., Finkelstein S., Rose D., Green K. Identification of severe acute respiratory syndrome in Canada. N. Engl. J. Med. 2003;348(20):1995–2005.
    1. Qin C., Wang J., Wei Q., She M., Marasco W.A., Jiang H. An animal model of SARS produced by infection of Macaca mulatta with SARS coronavirus. J. Pathol. 2005;206(3):251–259.
    1. Raj V.S., Mou H., Smits S.L., Dekkers D.H., Muller M.A., Dijkman R. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature. 2013;495(7440):251–254.
    1. Raj V.S., Smits S.L., Provacia L.B., van den Brand J.M., Wiersma L., Ouwendijk W.J. Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus. J. Virol. 2014;88(3):1834–1838.
    1. Reusken C.B., Haagmans B.L., Muller M.A., Gutierrez C., Godeke G.J., Meyer B. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect. Dis. 2013;13(10):859–866.
    1. Reusken C.B., Ababneh M., Raj V.S., Meyer B., Eljarah A., Abutarbush S. Middle East respiratory syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013. Eurosurveillance. 2013;18(50):20662.
    1. Roberts A., Subbarao K. Animal models for SARS. Adv. Exp. Med. Biol. 2006;581:463–471.
    1. Roberts A., Vogel L., Guarner J., Hayes N., Murphy B., Zaki S. Severe acute respiratory syndrome coronavirus infection of golden Syrian hamsters. J. Virol. 2005;79(1):503–511.
    1. Roberts A., Paddock C., Vogel L., Butler E., Zaki S., Subbarao K. Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans. J. Virol. 2005;79(9):5833–5838.
    1. Roberts A., Thomas W.D., Guarner J., Lamirande E.W., Babcock G.J., Greenough T.C. Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters. J. Infect. Dis. 2006;193(5):685–692.
    1. Roberts A., Deming D., Paddock C.D., Cheng A., Yount B., Vogel L. A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice. PLoS Pathog. 2007;3(1):e5.
    1. Roberts A., Lamirande E.W., Vogel L., Jackson J.P., Paddock C.D., Guarner J. Animal models and vaccines for SARS-CoV infection. Virus Res. 2008;133(1):20–32.
    1. Rockx B., Feldmann F., Brining D., Gardner D., LaCasse R., Kercher L. Comparative pathogenesis of three human and zoonotic SARS-CoV strains in cynomolgus macaques. PloS One. 2011;6(4):e18558.
    1. Rowe T., Gao G., Hogan R.J., Crystal R.G., Voss T.G., Grant R.L. Macaque model for severe acute respiratory syndrome. J. Virol. 2004;78(20):11401–11404.
    1. Ruan Y.J., Wei C.L., Ee A.L., Vega V.B., Thoreau H., Su S.T. Comparative full-length genome sequence analysis of 14 SARS coronavirus isolates and common mutations associated with putative origins of infection. Lancet. 2003;361(9371):1779–1785.
    1. Severe acute respiratory syndrome (SARS), 2003. Releve epidemiologique hebdomadaire/Section d׳hygiene du Secretariat de la Societe des Nations=Weekly epidemiological record/Health Section of the Secretariat of the League of Nations 78 (12), 81–83.
    1. Subbarao K., McAuliffe J., Vogel L., Fahle G., Fischer S., Tatti K. Prior infection and passive transfer of neutralizing antibody prevent replication of severe acute respiratory syndrome coronavirus in the respiratory tract of mice. J. Virol. 2004;78(7):3572–3577.
    1. Tsang K.W., Ho P.L., Ooi G.C., Yee W.K., Wang T., Chan-Yeung M. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N. Engl. J. Med. 2003;348(20):1977–1985.
    1. Tseng C.T., Huang C., Newman P., Wang N., Narayanan K., Watts D.M. Severe acute respiratory syndrome coronavirus infection of mice transgenic for the human angiotensin-converting enzyme 2 virus receptor. J. Virol. 2007;81(3):1162–1173.
    1. ter Meulen J., Bakker A.B., van den Brink E.N., Weverling G.J., Martina B.E., Haagmans B.L. Human monoclonal antibody as prophylaxis for SARS coronavirus infection in ferrets. Lancet. 2004;363(9427):2139–2141.
    1. van Boheemen S., de Graaf M., Lauber C., Bestebroer T.M., Raj V.S., Zaki A.M. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. mBio. 2012;3(6) e00473-12.
    1. van den Brand J.M., Haagmans B.L., Leijten L., van Riel D., Martina B.E., Osterhaus A.D. Pathology of experimental SARS coronavirus infection in cats and ferrets. Vet. Pathol. 2008;45(4):551–562.
    1. van Doremalen N., Miazgowicz K.L., Milne-Price S., Bushmaker T., Robertson S., Scott D. Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4. J. Virol. 2014;88(16):9220–9232.
    1. WHO, 2003a. Cumulative Number of Reported Probable Cases of SARS [updated July 11, 2003]. Available from: .
    1. WHO, 2003b. World Health Organization issues emergency travel advisory. Available from: .
    1. WHO, 2014. Middle East respiratory syndrome coronavirus (MERS-CoV) [updated May 9, 2014; cited December 11, 2014]. Available from: .
    1. Wang N., Shi X., Jiang L., Zhang S., Wang D., Tong P. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res. 2013;23(8):986–993.
    1. Watts D.M., Peters C.J., Newman P., Wang N., Yoshikawa N., Tseng C.K. Evaluation of cotton rats as a model for severe acute respiratory syndrome. Vector Borne Zoonotic Dis. 2008;8(3):339–344.
    1. Weingartl H., Czub M., Czub S., Neufeld J., Marszal P., Gren J. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. J. Virol. 2004;78(22):12672–12676.
    1. Wentworth D.E., Gillim-Ross L., Espina N., Bernard K.A. Mice susceptible to SARS coronavirus. Emerg. Infect. Dis. 2004;10(7):1293–1296.
    1. Wu D., Tu C., Xin C., Xuan H., Meng Q., Liu Y. Civets are equally susceptible to experimental infection by two different severe acute respiratory syndrome coronavirus isolates. J. Virol. 2005;79(4):2620–2625.
    1. Wu K., Chen L., Peng G., Zhou W., Pennell C.A., Mansky L.M. A virus-binding hot spot on human angiotensin-converting enzyme 2 is critical for binding of two different coronaviruses. J. Virol. 2011;85(11):5331–5337.
    1. Wu K., Peng G., Wilken M., Geraghty R.J., Li F. Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus. J. Biol. Chem. 2012;287(12):8904–8911.
    1. Yang X.H., Deng W., Tong Z., Liu Y.X., Zhang L.F., Zhu H. Mice transgenic for human angiotensin-converting enzyme 2 provide a model for SARS coronavirus infection. Comp. Med. 2007;57(5):450–459.
    1. Yang Z.Y., Kong W.P., Huang Y., Roberts A., Murphy B.R., Subbarao K. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice. Nature. 2004;428(6982):561–564.
    1. Yao Y., Bao L., Deng W., Xu L., Li F., Lv Q. An animal model of MERS produced by infection of rhesus macaques with MERS coronavirus. J. Infect. Dis. 2014;209(2):236–242.
    1. Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012;367(19):1814–1820.
    1. Zhang N., Jiang S., Du L. Current advancements and potential strategies in the development of MERS-CoV vaccines. Expert Revi. Vaccines. 2014;13(6):761–774.
    1. Zhang N. Receptor-binding domain-based subunit vaccines against MERS-CoV. Virus Res. 2014 doi: 10.1016/j.virusres.2014.11.013.
    1. Zhao J., Li K., Wohlford-Lenane C., Agnihothram S.S., Fett C., Zhao J. Rapid generation of a mouse model for Middle East respiratory syndrome. Proc. Natl. Acad. Sci. USA. 2014;111(13):4970–4975.
    1. Zhong N.S., Zheng B.J., Li Y.M., Poon, Xie Z.H., Chan K.H. Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People׳s Republic of China, in February, 2003. Lancet. 2003;362(9393):1353–1358.
    1. Zornetzer G.A., Frieman M.B., Rosenzweig E., Korth M.J., Page C., Baric R.S. Transcriptomic analysis reveals a mechanism for a prefibrotic phenotype in STAT1 knockout mice during severe acute respiratory syndrome coronavirus infection. J. Virol. 2010;84(21):11297–11309.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi