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. 2009 May 15;108(4):270–279. doi: 10.1016/S0929-6646(09)60066-8

Human Coronaviruses 229E and NL63: Close Yet Still So Far

Ronald Dijkman 1, Lia van der Hoek 1,*
PMCID: PMC7135404  PMID: 19369173

Abstract

HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.

Key Words: common cold, croup, human coronavirus 229E, human coronavirus NL63

References

  • 1.Lai MMC, Perlman S, Anderson JL. Coronaviridae. In: Knipe DM, Howley PM, editors. Fields Virology. 5th edition. Lippincott Williams & Wilkins; Philadelphia: 2006. pp. 1305–1335. [Google Scholar]
  • 2.Hamre D, Procknow JJ. A new virus isolated from the human respiratory tract. Proc Soc Exp Biol Med. 1966;121:190–193. doi: 10.3181/00379727-121-30734. [DOI] [PubMed] [Google Scholar]
  • 3.McIntosh K, Dees JH, Becker WB. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Proc Natl Acad Sci USA. 1967;57:933–940. doi: 10.1073/pnas.57.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Rota PA, Oberste MS, Monroe SS. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science. 2003;300:1394–1399. doi: 10.1126/science.1085952. [DOI] [PubMed] [Google Scholar]
  • 5.Drosten C, Gunther S, Preiser W. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348:1967–1976. doi: 10.1056/NEJMoa030747. [DOI] [PubMed] [Google Scholar]
  • 6.van der Hoek L, Pyrc K, Jebbink MF. Identification of a new human coronavirus. Nat Med. 2004;10:368–373. doi: 10.1038/nm1024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Woo PC, Lau SK, Huang Y. Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia. Arch Virol. 2005;150:2299–2311. doi: 10.1007/s00705-005-0573-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.van der Hoek L. Human coronaviruses: what do they cause? Antivir Ther. 2007;12:651–658. [PubMed] [Google Scholar]
  • 9.Li W, Shi Z, Yu M. Bats are natural reservoirs of SARS-like coronaviruses. Science. 2005;310:676–679. doi: 10.1126/science.1118391. [DOI] [PubMed] [Google Scholar]
  • 10.Tang XC, Zhang JX, Zhang SY. Prevalence and genetic diversity of coronaviruses in bats from China. J Virol. 2006;80:7481–7490. doi: 10.1128/JVI.00697-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Zhang J, Guy JS, Snijder EJ. Genomic characterization of equine coronavirus. Virol. 2007;369:92–104. doi: 10.1016/j.virol.2007.06.035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Woo PC, Wang M, Lau SK. Comparative analysis of twelve genomes of three novel group 2c and group 2d coronaviruses reveals unique group and subgroup features. J Virol. 2007;81:1574–1585. doi: 10.1128/JVI.02182-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Dong BQ, Liu W, Fan XH. Detection of a novel and highly divergent coronavirus from Asian leopard cats and Chinese ferret badgers in Southern China. J Virol. 2007;81:6920–6926. doi: 10.1128/JVI.00299-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Lau SK, Woo PC, Li KS. Complete genome sequence of bat coronavirus HKU2 from Chinese horseshoe bats revealed a much smaller spike gene with a different evolutionary lineage from the rest of the genome. Virology. 2007;367:428–439. doi: 10.1016/j.virol.2007.06.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Mihindukulasuriya KA, Wu G, St Leger J. Identification of a novel coronavirus from a beluga whale by using a panviral microarray. J Virol. 2008;82:5084–5088. doi: 10.1128/JVI.02722-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Chu DK, Peiris JS, Chen H. Genomic characterizations of bat coronaviruses (1A, 1B and HKU8) and evidence for co-infections in Miniopterus bats. J Gen Virol. 2008;89:1282–1287. doi: 10.1099/vir.0.83605-0. [DOI] [PubMed] [Google Scholar]
  • 17.Larkin MA, Blackshields G, Brown NP. Clustal W and Clustal X version 2.0. Bioinformatics. 2007;23:2947–2948. doi: 10.1093/bioinformatics/btm404. [DOI] [PubMed] [Google Scholar]
  • 18.Tamura K, Dudley J, Nei M. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol. 2007;24:1596–1599. doi: 10.1093/molbev/msm092. [DOI] [PubMed] [Google Scholar]
  • 19.Wang LF, Eaton BT. Bats, civets and the emergence of SARS. Curr Top Microbiol Immunol. 2007;315:325–344. doi: 10.1007/978-3-540-70962-6_13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Doyle LP, Hutchings LM. A transmissible gastroenteritis in pigs. J Am Vet Med Assoc. 1946;108:257–259. [PubMed] [Google Scholar]
  • 21.Almeida JD, Tyrrell DA. The morphology of three previously uncharacterized human respiratory viruses that grow in organ culture. J Gen Virol. 1967;1:175–178. doi: 10.1099/0022-1317-1-2-175. [DOI] [PubMed] [Google Scholar]
  • 22.Binn LN, Lazar EC, Keenan KP. Recovery and characterization of a coronavirus from military dogs with diarrhea. Proc Annu Meet U S Anim Health Assoc. 1974;78:359–366. [PubMed] [Google Scholar]
  • 23.Pensaert MB, de Bouck P. A new coronavirus-like particle associated with diarrhea in swine. Arch Virol. 1978;58:243–247. doi: 10.1007/BF01317606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Evermann JF, Baumgartener L, Ott RL. Characterization of a feline infectious peritonitis virus isolate. Vet Pathol. 1981;18:256–265. doi: 10.1177/030098588101800214. [DOI] [PubMed] [Google Scholar]
  • 25.Pensaert M, Callebaut P, Vergote J. Isolation of a porcine respiratory, non-enteric coronavirus related to transmissible gastroenteritis. Vet Q. 1986;8:257–261. doi: 10.1080/01652176.1986.9694050. [DOI] [PubMed] [Google Scholar]
  • 26.Fouchier RA, Hartwig NG, Bestebroer TM. A previously undescribed coronavirus associated with respiratory disease in humans. Proc Natl Acad Sci USA. 2004;101:6212–6216. doi: 10.1073/pnas.0400762101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Herrewegh AA, Vennema H, Horzinek MC. The molecular genetics of feline coronaviruses: comparative sequence analysis of the ORF7a/7b transcription unit of different biotypes. Virology. 1995;212:622–631. doi: 10.1006/viro.1995.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Haijema BJ, Volders H, Rottier PJ. Live, attenuated coro-navirus vaccines through the directed deletion of group-specific genes provide protection against feline infectious peritonitis. J Virol. 2004;78:3863–3871. doi: 10.1128/JVI.78.8.3863-3871.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Song DS, Yang JS, Oh JS. Differentiation of a Vero cell adapted porcine epidemic diarrhea virus from Korean field strains by restriction fragment length polymorphism analysis of ORF 3. Vaccine. 2003;21:1833–1842. doi: 10.1016/S0264-410X(03)00027-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Woods RD. Efficacy of a transmissible gastroenteritis coro-navirus with an altered ORF-3 gene. Can J Vet Res. 2001;65:28–32. [PMC free article] [PubMed] [Google Scholar]
  • 31.Dijkman R, Jebbink MF, Wilbrink B. Human corona-virus 229E encodes a single ORF4 protein between the spike and the envelope genes. Virol J. 2006;3:106. doi: 10.1186/1743-422X-3-106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 32.Thiel V, Herold J, Schelle B. Infectious RNA transcribed in vitro from a cDNA copy of the human corona-virus genome cloned in vaccinia virus. J Gen Virol. 2001;82:1273–1281. doi: 10.1099/0022-1317-82-6-1273. [DOI] [PubMed] [Google Scholar]
  • 33.Chibo D, Birch C. Analysis of human coronavirus 229E spike and nucleoprotein genes demonstrates genetic drift between chronologically distinct strains. J Gen Virol. 2006;87:1203–1208. doi: 10.1099/vir.0.81662-0. [DOI] [PubMed] [Google Scholar]
  • 34.Pyrc K, Dijkman R, Deng L. Mosaic structure of human coronavirus NL63, one thousand years of evolution. J Mol Biol. 2006;364:964–973. doi: 10.1016/j.jmb.2006.09.074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Liu C, Feng Y, Gao F. Characterization of HCoV–229E fusion core: implications for structure basis of coronavirus membrane fusion. Biochem Biophys Res Commun. 2006;345:1108–1115. doi: 10.1016/j.bbrc.2006.04.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Zheng Q, Deng Y, Liu J. Core structure of S2 from the human coronavirus NL63 spike glycoprotein. Biochem. 2006;45:15205–15215. doi: 10.1021/bi061686w. [DOI] [PubMed] [Google Scholar]
  • 37.Pyrc K, Berkhout B, van der Hoek L. Recent Research Developments in Infection and Immunity. 3rd edition. Transworld Research Network; Kerala, India: 2005. Molecular characterization of human coronavirus NL63; pp. 25–48. [Google Scholar]
  • 38.Hofmann H, Simmons G, Rennekamp AJ. Highly conserved regions within the spike proteins of human coronaviruses 229E and NL63 determine recognition of their respective cellular receptors. J Virol. 2006;80:8639–8652. doi: 10.1128/JVI.00560-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Lin HX, Feng Y, Wong G. Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction. J Gen Virol. 2008;89:1015–1024. doi: 10.1099/vir.0.83331-0. [DOI] [PubMed] [Google Scholar]
  • 40.Bonavia A, Zelus BD, Wentworth DE. Identification of a receptor-binding domain of the spike glycoprotein of human coronavirus HCoV–229E. J Virol. 2003;77:2530–2538. doi: 10.1128/JVI.77.4.2530-2538.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Yeager CL, Ashmun RA, Williams RK. Human ami-nopeptidase N is a receptor for human coronavirus 229E. Nature. 1992;357:420–422. doi: 10.1038/357420a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Smith MK, Tusell S, Travanty EA. Human angiotensin-converting enzyme 2 (ACE2) is a receptor for human respiratory coronavirus NL63. Adv Exp Med Biol. 2006;581:285–288. doi: 10.1007/978-0-387-33012-9_48. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Hofmann H, Pyrc K, van der Hoek L. Human coro-navirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci USA. 2005;102:7988–7993. doi: 10.1073/pnas.0409465102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Kolb AF, Maile J, Heister A. Characterization of functional domains in the human coronavirus HCV 229E receptor. J Gen Virol. 1996;77:2515–2521. doi: 10.1099/0022-1317-77-10-2515. [DOI] [PubMed] [Google Scholar]
  • 45.Wang G, Deering C, Macke M. Human coronavirus 229E infects polarized airway epithelia from the apical surface. J Virol. 2000;74:9234–9239. doi: 10.1128/jvi.74.19.9234-9239.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Mina-Osorio P. The moonlighting enzyme CD13: old and new functions to target. Trends Mol Med. 2008;14:361–371. doi: 10.1016/j.molmed.2008.06.003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Hamming I, Timens W, Bulthuis ML. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogen-esis. J Pathol. 2004;203:631–637. doi: 10.1002/path.1570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Karamyan VT, Speth RC. Enzymatic pathways of the brain renin-angiotensin system: unsolved problems and continuing challenges. Regul Pept. 2007;143:15–27. doi: 10.1016/j.regpep.2007.03.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Oh JS, Song DS, Park BK. Identification of a putative cellular receptor 150 kDa polypeptide for porcine epidemic diarrhea virus in porcine enterocytes. J Vet Sci. 2003;4:269–275. [PubMed] [Google Scholar]
  • 50.Li BX, Ge JW, Li YJ. Porcine aminopeptidase N is a functional receptor for the PEDV coronavirus. Virol. 2007;365:166–172. doi: 10.1016/j.virol.2007.03.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Delmas B, Gelfi J, L'Haridon R. Aminopeptidase N is a major receptor for the entero-pathogenic coronavirus TGEV. Nature. 1992;357:417–420. doi: 10.1038/357417a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Tresnan DB, Levis R, Holmes KV. Feline aminopeptidase N serves as a receptor for feline, canine, porcine, and human coronaviruses in serogroup I. J Virol. 1996;70:8669–8674. doi: 10.1128/jvi.70.12.8669-8674.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Li W, Moore MJ, Vasilieva N. Angiotensin-converting enzyme 2 is a functional receptor for the SARS corona-virus. Nature. 2003;426:450–454. doi: 10.1038/nature02145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Kuba K, Imai Y, Rao S. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005;11:875–879. doi: 10.1038/nm1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55.Lachance C, Arbour N, Cashman NR. Involvement of aminopeptidase N (CD13) in infection of human neural cells by human coronavirus 229E. J Virol. 1998;72:6511–6519. doi: 10.1128/jvi.72.8.6511-6519.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Freymuth F, Vabret A, Cuvillon-Nimal D. Comparison of multiplex PCR assays and conventional techniques for the diagnostic of respiratory virus infections in children admitted to hospital with an acute respiratory illness. J Med Virol. 2006;78:1498–1504. doi: 10.1002/jmv.20725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Schildgen O, Jebbink MF, de Vries M. Identification of cell lines permissive for human coronavirus NL63. J Virol Methods. 2006;138:207–210. doi: 10.1016/j.jviromet.2006.07.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Sims AC, Baric RS, Yount B. Severe acute respiratory syndrome coronavirus infection of human ciliated airway epithelia: role of ciliated cells in viral spread in the conducting airways of the lungs. J Virol. 2005;79:15511–15524. doi: 10.1128/JVI.79.24.15511-15524.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Lassnig C, Sanchez CM, Egerbacher M. Development of a transgenic mouse model susceptible to human coronavirus 229E. Proc Natl Acad Sci USA. 2005;102:8275–8280. doi: 10.1073/pnas.0408589102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Lassnig C, Kolb A, Strobl B. Studying human pathogens in animal models: fine tuning the humanized mouse. Transgenic Res. 2005;14:803–806. doi: 10.1007/s11248-005-1676-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Wentworth DE, Tresnan DB, Turner BC. Cells of human aminopeptidase N (CD13) transgenic mice are infected by human coronavirus–229E in vitro, but not in vivo. Virol. 2005;335:185–197. doi: 10.1016/j.virol.2005.02.023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Han TH, Chung JY, Kim SW. Human Coronavirus-NL63 infections in Korean children, 2004–2006. J Clin Virol. 2007;38:27–31. doi: 10.1016/j.jcv.2006.10.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Arden KE, Nissen MD, Sloots TP. New human coro-navirus, HCoV-NL63, associated with severe lower respiratory tract disease in Australia. J Med Virol. 2005;75:455–462. doi: 10.1002/jmv.20288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 64.Bastien N, Anderson K, Hart L. Human coronavirus NL63 infection in Canada. J Infect Dis. 2005;191:503–506. doi: 10.1086/426869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.van Elden LJ, van Loon AM, van Alphen F. Frequent detection of human coronaviruses in clinical specimens from patients with respiratory tract infection by use of a novel real-time reverse-transcriptase polymerase chain reaction. J Infect Dis. 2004;189:652–657. doi: 10.1086/381207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Dijkman R, Jebbink MF, El Idrissi NB. Human coro-navirus NL63 and 229E seroconversion in children. J Clin Microbiol. 2008;46:2368–2373. doi: 10.1128/JCM.00533-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Shao X, Guo X, Esper F. Seroepidemiology of group I human coronaviruses in children. J Clin Virol. 2007;40:207–213. doi: 10.1016/j.jcv.2007.08.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Gerna G, Percivalle E, Sarasini A. Human respiratory coronavirus HKU1 versus other coronavirus infections in Italian hospitalised patients. J Clin Virol. 2007;38:244–250. doi: 10.1016/j.jcv.2006.12.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Vabret A, Dina J, Gouarin S. Human (non-severe acute respiratory syndrome) coronavirus infections in hospitalised children in France. J Paediatr Child Health. 2007;44:176–181. doi: 10.1111/j.1440-1754.2007.01246.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.van der Hoek L, Sure K, Ihorst G. Croup is associated with the novel coronavirus NL63. PLoS Med. 2005;2:e240. doi: 10.1371/journal.pmed.0020240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Callow KA, Parry HF, Sergeant M. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect. 1990;105:435–446. doi: 10.1017/s0950268800048019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 72.Bradburne AF, Bynoe ML, Tyrrell DA. Effects of a “new” human respiratory virus in volunteers. Br Med J. 1967;3:767–769. doi: 10.1136/bmj.3.5568.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Kapikian AZ, James HD, Jr, Kelly SJ. Isolation from man of “avian infectious bronchitis virus-like” viruses (coronaviruses) similar to 229E virus, with some epidemi-ological observations. J Infect Dis. 1969;119:282–290. doi: 10.1093/infdis/119.3.282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Wu PS, Chang LY, Berkhout B. Clinical manifestations of human coronavirus NL63 infection in children in Taiwan. Eur J Pediatr. 2008;167:75–80. doi: 10.1007/s00431-007-0429-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Choi EH, Lee HJ, Kim SJ. The association of newly identified respiratory viruses with lower respiratory tract infections in Korean children, 2000–2005. Clin Infect Dis. 2006;43:585–592. doi: 10.1086/506350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Esper F, Shapiro ED, Weibel C. Association between a novel human coronavirus and Kawasaki Disease. J Infect Dis. 2005;191:499–502. doi: 10.1086/428291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Burns JC, Glode MP. Kawasaki syndrome. Lancet. 2004;364:533–544. doi: 10.1016/S0140-6736(04)16814-1. [DOI] [PubMed] [Google Scholar]
  • 78.Chang LY, Chiang BL, Kao CL. Lack of association between infection with a novel human coronavirus (HCoV), HCoV-NH, and Kawasaki Disease in Taiwan. J Infect Dis. 2006;193:283–286. doi: 10.1086/498875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Dominguez SR, Anderson MS, Glode MP. Blinded case-control study of the relationship between human coronavirus NL63 and Kawasaki syndrome. J Infect Dis. 2006;194:1697–1701. doi: 10.1086/509509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Baker SC, Shimizu C, Shike H. Human coronavirus-NL63 infection is not associated with acute Kawasaki disease. Adv Exp Med Biol. 2006;581:523–526. doi: 10.1007/978-0-387-33012-9_94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.Shimizu C, Shike H, Baker SC. Human coronavirus NL63 is not detected in the respiratory tracts of children with acute Kawasaki Disease. J Infect Dis. 2005;192:1767–1771. doi: 10.1086/497170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Ebihara T, Endo R, Ma X. Lack of association between New Haven coronavirus and Kawasaki disease. J Infect Dis. 2005;192:351–352. doi: 10.1086/430797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Burks JS, DeVald BL, Jankovsky LD. Two corona-viruses isolated from central nervous system tissue of two multiple sclerosis patients. Science. 1980;209:933–934. doi: 10.1126/science.7403860. [DOI] [PubMed] [Google Scholar]
  • 84.Murray RS, Brown B, Brian D. Detection of corona-virus RNA and antigen in multiple sclerosis brain. Ann Neurol. 1992;31:525–533. doi: 10.1002/ana.410310511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Arbour N, Day R, Newcombe J. Neuroinvasion by human respiratory coronaviruses. J Virol. 2000;74:8913–8921. doi: 10.1128/jvi.74.19.8913-8921.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Dessau RB, Lisby G, Frederiksen JL. Coronaviruses in brain tissue from patients with multiple sclerosis. Acta Neuropathol (Berl) 2001;101:601–604. doi: 10.1007/s004010000331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Pyrc K, Bosch BJ, Berkhout B. Inhibition of HCoV-NL63 infection at early stages of the replication cycle. Antim Ag Chemoth. 2006;50:2000–2008. doi: 10.1128/AAC.01598-05. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Cavallaro JJ, Monto AS. Community-wide outbreak of infection with a 229E-like coronavirus in Tecumseh, Michigan. J Infect Dis. 1970;122:272–279. doi: 10.1093/infdis/122.4.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Gurcan HM, Ahmed AR. Efficacy of various intravenous immunoglobulin therapy protocols in autoimmune and chronic inflammatory disorders. Ann Pharmacother. 2007;41:812–823. doi: 10.1345/aph.1K037. [DOI] [PubMed] [Google Scholar]
  • 90.Haller O, Weber F. Pathogenic viruses: smart manipulators of the interferon system. Curr Top Microbiol Immunol. 2007;316:315–334. doi: 10.1007/978-3-540-71329-6_15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Hertzig T, Scandella E, Schelle B. Rapid identification of coronavirus replicase inhibitors using a selectable replicon RNA. J Gen Virol. 2004;85:1717–1725. doi: 10.1099/vir.0.80044-0. [DOI] [PubMed] [Google Scholar]
  • 92.Tyrrell DA. The efficacy and tolerance of intranasal inter-ferons: studies at the Common Cold Unit. J Antimicrob Chemother. 1986;18(Suppl B):153–156. doi: 10.1093/jac/18.Supplement_B.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Haasnoot J, Westerhout EM, Berkhout B. RNA interference against viruses: strike and counterstrike. Nat Biotechnol. 2007;25:1435–1443. doi: 10.1038/nbt1369. [DOI] [PMC free article] [PubMed] [Google Scholar]

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