Coronaviruses*

Naomi J. Gadsby; Kate E. Templeton

doi:10.1128/9781555817381.ch90

Chapter 90 : Coronaviruses*

Authors: Naomi J. Gadsby, Kate E. Templeton

Content Type: Reference

Publication Year: 2015

Category: Clinical Microbiology

Book DOI: 10.1128/9781555817381

Chapter DOI: 10.1128/9781555817381.ch90

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Coronaviruses*, Page 1 of 2

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Abstract:

Coronaviruses (CoV) are enveloped viruses with large RNA genomes and are found in several animal species, including humans. Four coronaviruses HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 are endemic in humans and associated with a range of upper and lower respiratory tract disease from the common cold to severe pneumonia. HCoVs make up a small but significant proportion of the viruses found in patients with acute respiratory illness (ARI), particularly in children and during the winter and spring months. The highly pathogenic CoVs responsible for severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome (MERS-CoV) have only recently emerged in the human population through zoonotic transmission. SARS-CoV has not been reported since early 2004 but caused significant morbidity and mortality during a global outbreak in 2002/2003. Since 2012, MERS-CoV has caused a number of cases of severe ARI linked to the Arabian Peninsula and transmission is still occurring. Isolation of CoVs is not effective as a routine diagnostic tool because many commonly used cell lines are not permissive for growth and cytopathic effect is generally nonspecific. Reagents for immunofluorescent detection are not widely available and serological testing is most useful for epidemiological studies and retrospective diagnosis. Direct detection of CoV nucleic acid in clinical specimens is the most common diagnostic method currently in use. A range of in-house RT-PCR methods have been developed for either pan-CoV or species-specific detection, and commercial nucleic acid amplification tests (NAATs) are also now available.

Citation: Gadsby N, Templeton K. 2015. Coronaviruses*, p 1565-1583. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch90

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Coronaviruses*

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FIGURE 1

Electron micrograph of HCoV-OC43 showing pleomorphic shape and characteristic coronas made up of surrounding peplomers. doi:10.1128/9781555817381.ch90.f1

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10.1128/9781555817381/9781555817381.ch90.f1.gif

FIGURE 1

Electron micrograph of HCoV-OC43 showing pleomorphic shape and characteristic coronas made up of surrounding peplomers. doi:10.1128/9781555817381.ch90.f1

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FIGURE 2

Phylogenetic relationships among members of the subfamily Coronavirinae. A rooted neighbor-joining tree was generated from amino acid sequence alignments of the replicase proteins encoded by polymerase ORF1b for 20 CoVs, each a representative of a currently recognized CoV species, and for the newly recognized MERS-CoV strain Hu/Jordan-N3/2012; bovine torovirus strain Breda served as an out-group. Only bootstrap values equal to or larger than 95% are indicated. Virus names are given with strain specifications between parentheses; species and genus names are in italics as per convention. The tree shows the four main monophyletic clusters, corresponding to genera Alpha-, Beta-, Gamma-, and Deltacoronavirus. Also indicated are Betacoronavirus lineages A through D (corresponding to former CoV subgroups 2A through D). (Modified from reference 3 , kindly provided by RJ de Groot, and used with permission). doi:10.1128/9781555817381.ch90.f2

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FIGURE 2

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FIGURE 3

HCoV cytopathic effect at 5 days postinfection. (A) Uninfected LLC-MK2 cells. (B) HCoV-NL63-infected LLC-MK2 cells. doi:10.1128/9781555817381.ch90.f3

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FIGURE 3

HCoV cytopathic effect at 5 days postinfection. (A) Uninfected LLC-MK2 cells. (B) HCoV-NL63-infected LLC-MK2 cells. doi:10.1128/9781555817381.ch90.f3

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FIGURE 4

HCoV detection frequencies by month and age band over a 3-year period between 2006 and 2009 in Edinburgh, United Kingdom, using multiplex real-time RT-PCR. During this time, 11,661 specimens were tested, with 61 specimens positive for HCoV-HKU1, 99 for HCoV-OC43, 35 for HCoV-229E, and 75 for HCoV-NL63 (adapted from reference 39 ). doi:10.1128/9781555817381.ch90.f4

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FIGURE 4

References

/content/book/10.1128/9781555817381.mcm11.ch90

1. Adams MJ,, Carstens EB. 2012. Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2012). Arch Virol 157: 1411– 1422.

2. de Groot RJ,, Baker SC,, Baric RS,, Enjuanes L,, Gorbalenya AE,, Holmes KV,, Perlman S,, Poon L,, Rottier PJM,, Talbot PJ,, Woo PCY,, Ziebuhr J,. 2012. Family Coronaviridae, p 806– 828. In King AMQ,, Adams MJ,, Carstens EB,, Lefkowitz EJ ( ed), Virus Taxonomy: The Ninth Report of the International Committee on Taxonomy of Viruses. Academic Press, San Diego, CA.

3. de Groot RJ,, Baker SC,, Baric RS,, Brown CS,, Drosten C,, Enjuanes L,, Fouchier RA,, Galiano M,, Gorbalenya AE,, Memish Z,, Perlman S,, Poon LL,, Snijder EJ,, Stephens GM,, Woo PC,, Zaki AM,, Zambon M,, Ziebuhr J. 2013. Middle East respiratory syndrome coronavirus (MERS-CoV); announcement of the Coronavirus Study Group. J Virol 87: 7790– 7792.

4. van Boheemen S,, de Graaf M,, Lauber C,, Bestebroer TM,, Raj VS,, Zaki AM,, Osterhaus AD,, Haagmans BL,, Gorbalenya AE,, Snijder EJ,, Fouchier RA. 2012. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio 3: e00473– 00512.

5. Woo PC,, Lau SK,, Lam CS,, Lai KK,, Huang Y,, Lee P,, Luk GS,, Dyrting KC,, Chan KH,, Yuen KY. 2009. Comparative analysis of complete genome sequences of three avian coronaviruses reveals a novel group 3c coronavirus. J Virol 83: 908– 917.

6. Woo PC,, Lau SK,, Lam CS,, Lau CC,, Tsang AK,, Lau JH,, Bai R,, Teng JL,, Tsang CC,, Wang M,, Zheng BJ,, Chan KH,, Yuen KY. 2012. Discovery of seven novel mammalian and avian coronaviruses in the genus deltacoronavirus supports bat coronaviruses as the gene source of alphacoronavirus and betacoronavirus and avian coronaviruses as the gene source of gammacoronavirus and deltacoronavirus. J Virol 86: 3995– 4008.

7. Perlman S,, Netland J. 2009. Coronaviruses post-SARS: update on replication and pathogenesis. Nat Rev Microbiol 7: 439– 450.

8. Raj VS,, Mou H,, Smits SL,, Dekkers DH,, Müller MA,, Dijkman R,, Muth D,, Demmers JA,, Zaki A,, Fouchier RA,, Thiel V,, Drosten C,, Rottier PJ,, Osterhaus AD,, Bosch BJ,, Haagmans BL. 2013. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 495: 251– 254.

9. Pyrc K,, Dijkman R,, Deng L,, Jebbink MF,, Ross HA,, Berkhout B,, van der Hoek L. 2006. Mosaic structure of human coronavirus NL63, one thousand years of evolution. J Mol Biol 364: 964– 973.

10. van der Hoek L,, Pyrc K,, Jebbink MF,, Vermeulen-Oost W,, Berkhout RJ,, Wolthers KC,, Wertheim-van Dillen PM,, Kaandorp J,, Spaargaren J,, Berkhout B. 2004. Identification of a new human coronavirus. Nat Med 10: 368– 373.

11. Dijkman R,, van der Hoek L. 2009. Human coronaviruses 229E and NL63: close yet still so far. J Formos Med Assoc 108: 270– 279.

12. Huynh J,, Li S,, Yount B,, Smith A,, Sturges L,, Olsen JC,, Nagel J,, Johnson JB,, Agnihothram S,, Gates JE,, Frieman MB,, Baric RS,, Donaldson EF. 2012. Evidence supporting a zoonotic origin of human coronavirus strain NL63. J Virol 86: 12816– 12825.

13. Pfefferle S,, Oppong S,, Drexler JF,, Gloza-Rausch F,, Ipsen A,, Seebens A,, Müller MA,, Annan A,, Vallo P,, Adu-Sarkodie Y,, Kruppa TF,, Drosten C. 2009. Distant relatives of severe acute respiratory syndrome coronavirus and close relatives of human coronavirus 229E in bats, Ghana. Emerg Infect Dis 15: 1377– 1384.

14. Vijgen L,, Keyaerts E,, Lemey P,, Maes P,, van Reeth K,, Nauwynck H,, Pensaert M,, van Ranst M. 2006. Evolutionary history of the closely related group 2 coronaviruses: porcine hemagglutinating encephalomyelitis virus, bovine coronavirus, and human coronavirus OC43. J Virol 80: 7270– 7274.

15. Woo PC,, Lau SK,, Yip CC,, Huang Y,, Yuen KY. 2009. More and more coronaviruses: human coronavirus HKU1. Viruses 1: 57– 71.

16. Li W,, Shi Z,, Yu M,, Ren W,, Smith C,, Epstein JH,, Wang H,, Crameri G,, Hu Z,, Zhang H,, Zhang J,, McEachern J,, Field H,, Daszak P,, Eaton BT,, Zhang S,, Wang LF. 2005. Bats are natural reservoirs of SARS-like coronaviruses. Science 310: 676– 679.

17. Yip CW,, Hon CC,, Shi M,, Lam TT,, Chow KY,, Zeng F,, Leung FC. 2009. Phylogenetic perspectives on the epidemiology and origins of SARS and SARS-like coronaviruses. Infect Genet Evol 9: 1185– 1196.

18. Ithete NL,, Stoffberg S,, Corman VM,, Cottontail VM,, Richards LR,, Schoeman MC,, Drosten C,, Drexler JF,, Preiser W. 2013. Close relative of human Middle East respiratory syndrome coronavirus in bat, South Africa. Emerg Infect Dis 19: 1697– 1699.

19. Memish ZA,, Mishra N,, Olival KJ,, Fagbo SF,, Kapoor V,, Epstein JH,, Alhakeem R,, Durosinloun A,, Al Asmari M,, Islam A,, Kapoor A,, Briese T,, Daszak P,, Al Rabeeah AA,, Lipkin WI. 2013. Middle East respiratory syndrome coronavirus in bats, Saudi Arabia. Emerg Infect Dis 19: 1819– 1823.

20. Reusken CB,, Haagmans BL,, Müller MA,, Gutierrez C,, Godeke GJ,, Meyer B,, Muth D,, Raj VS,, Smits-De Vries L,, Corman VM,, Drexler JF,, Smits SL,, El Tahir YE,, De Sousa R,, van Beek J,, Nowotny N,, van Maanen K,, Hidalgo-Hermoso E,, Bosch BJ,, Rottier P,, Osterhaus A,, Gortázar-Schmidt C,, Drosten C,, Koopmans MP. 2013. Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study. Lancet Infect Dis 13: 859– 866.

21. Perera RA,, Wang P,, Gomaa MR,, El-Shesheny R,, Kandeil A,, Bagato O,, Siu LY,, Shehata MM,, Kayed AS,, Moatasim Y,, Li M,, Poon LL,, Guan Y,, Webby RJ,, Ali MA,, Peiris JS,, Kayali G. 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. Euro Surveill 18: 20574.

22. Cotten M,, Watson SJ,, Kellam P,, Al-Rabeeah AA,, Makhdoom HQ,, Assiri A,, Al-Tawfiq JA,, Alhakeem RF,, Madani H,, Alrabiah FA,, Al-Hajjar S,, Al-Nassir WN,, Albarrak A,, Flemban H,, Balkhy HH,, Alsubaie S,, Palser AL,, Gall A,, Bashford-Rogers R,, Rambaut A,, Zumla AI,, Memish ZA. 2013. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet 382: 1993– 2002.

23. Hamre D,, Procknow JJ. 1966. A new virus isolated from the human respiratory tract. Proc Soc Exp Biol Med 121: 190– 193.

24. McIntosh K,, Dees JH,, Becker WB,, Kapikian AZ,, Chanock RM. 1967. Recovery in tracheal organ cultures of novel viruses from patients with respiratory disease. Proc Natl Acad Sci USA 57: 933– 940.

25. Tyrrell DA,, Bynoe ML. 1965. Cultivation of a novel type of common-cold virus in organ cultures. Br Med J 1: 1467– 1470.

26. Brucková M,, McIntosh K,, Kapikian AZ,, Chanock RM. 1970. The adaptation of two human coronavirus strains (OC38 and OC43) to growth in cell monolayers. Proc Soc Exp Biol Med 135: 431– 435.

27. Drosten C,, Günther S,, Preiser W,, van der Werf S,, Brodt HR,, Becker S,, Rabenau H,, Panning M,, Kolesnikova L,, Fouchier RA,, Berger A,, Burguière AM,, Cinatl J,, Eickmann M,, Escriou N,, Grywna K,, Kramme S,, Manuguerra JC,, Müller S,, Rickerts V,, Stürmer M,, Vieth S,, Klenk HD,, Osterhaus AD,, Schmitz H,, Doerr HW. 2003. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 348: 1967– 1976.

28. Ksiazek TG,, Erdman D,, Goldsmith CS,, Zaki SR,, Peret T,, Emery S,, Tong S,, Urbani C,, Comer JA,, Lim W,, Rollin PE,, Dowell SF,, Ling AE,, Humphrey CD,, Shieh WJ,, Guarner J,, Paddock CD,, Rota P,, Fields B,, DeRisi J,, Yang JY,, Cox N,, Hughes JM,, LeDuc JW,, Bellini WJ,, Anderson LJ; SARS Working Group. 2003. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348: 1953– 1966.

29. Marra MA,, Jones SJ,, Astell CR,, Holt RA,, Brooks-Wilson A,, Butterfield YS,, Khattra J,, Asano JK,, Barber SA,, Chan SY,, Cloutier A,, Coughlin SM,, Freeman D,, Girn N,, Griffith OL,, Leach SR,, Mayo M,, McDonald H,, Montgomery SB,, Pandoh PK,, Petrescu AS,, Robertson AG,, Schein JE,, Siddiqui A,, Smailus DE,, Stott JM,, Yang GS,, Plummer F,, Andonov A,, Artsob H,, Bastien N,, Bernard K,, Booth TF,, Bowness D,, Czub M,, Drebot M,, Fernando L,, Flick R,, Garbutt M,, Gray M,, Grolla A,, Jones S,, Feldmann H,, Meyers A,, Kabani A,, Li Y,, Normand S,, Stroher U,, Tipples GA,, Tyler S,, Vogrig R,, Ward D,, Watson B,, Brunham RC,, Krajden M,, Petric M,, Skowronski DM,, Upton C,, Roper RL. 2003. The genome sequence of the SARS-associated coronavirus. Science 300: 1399– 1404.

30. Peiris JS,, Lai ST,, Poon LL,, Guan Y,, Yam LY,, Lim W,, Nicholls J,, Yee WK,, Yan WW,, Cheung MT,, Cheng VC,, Chan KH,, Tsang DN,, Yung RW,, Ng TK,, Yuen KY; SARS study group. 2003. Coronavirus as a possible cause of severe acute respiratory syndrome. Lancet 361: 1319– 1325.

31. Poutanen SM,, Low DE,, Henry B,, Finkelstein S,, Rose D,, Green K,, Tellier R,, Draker R,, Adachi D,, Ayers M,, Chan AK,, Skowronski DM,, Salit I,, Simor AE,, Slutsky AS,, Doyle PW,, Krajden M,, Petric M,, Brunham RC,, McGeer AJ; National Microbiology Laboratory, Canada; Canadian Severe Acute Respiratory Syndrome Study Team. 2003. Identification of severe acute respiratory syndrome in Canada. N Engl J Med 348: 1995– 2005.

32. Rota PA,, Oberste MS,, Monroe SS,, Nix WA,, Campagnoli R,, Icenogle JP,, Peñaranda S,, Bankamp B,, Maher K,, Chen MH,, Tong S,, Tamin A,, Lowe L,, Frace M,, DeRisi JL,, Chen Q,, Wang D,, Erdman DD,, Peret TC,, Burns C,, Ksiazek TG,, Rollin PE,, Sanchez A,, Liffick S,, Holloway B,, Limor J,, McCaustland K,, Olsen-Rasmussen M,, Fouchier R,, Günther S,, Osterhaus AD,, Drosten C,, Pallansch MA,, Anderson LJ,, Bellini WJ. 2003. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science 300: 1394– 1399.

33. Fouchier RA,, Kuiken T,, Schutten M,, van Amerongen G,, van Doornum GJ,, van den Hoogen BG,, Peiris M,, Lim W,, Stohr K,, Osterhaus AD. 2003. Aetiology: Koch’s postulates fulfilled for SARS virus. Nature 423: 240.

34. Woo PC,, Lau SK,, Chu CM,, Chan KH,, Tsoi HW,, Huang Y,, Wong BH,, Poon RW,, Cai JJ,, Luk WK,, Poon LL,, Wong SS,, Guan Y,, Peiris JS,, Yuen KY. 2005. Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia. J Virol 79: 884– 895.

35. Talbot HK,, Shepherd BE,, Crowe JE Jr,, Griffin MR,, Edwards KM,, Podsiad AB,, Tollefson SJ,, Wright PF,, Williams JV. 2009. The pediatric burden of human coronaviruses evaluated for twenty years. Pediatr Infect Dis J 28: 682– 687.

36. Zaki AM,, van Boheemen S,, Bestebroer TM,, Osterhaus AD,, Fouchier RA. 2012. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 367: 1814– 1820.

37. Munster VJ,, de Wit E,, Feldmann H. 2013. Pneumonia from human coronavirus in a macaque model. N Engl J Med 368: 1560– 1562.

38. Cabeça TK,, Granato C,, Bellei N. 2013. Epidemiological and clinical features of human coronavirus infections among different subsets of patients. Influenza Other Respir Viruses 7: 1040– 1047.

39. Gaunt ER,, Hardie A,, Claas EC,, Simmonds P,, Templeton KE. 2010. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol 48: 2940– 2947.

40. Lu R,, Yu X,, Wang W,, Duan X,, Zhang L,, Zhou W,, Xu J,, Xu L,, Hu Q,, Lu J,, Ruan L,, Wang Z,, Tan W. 2012. Characterization of human coronavirus etiology in Chinese adults with acute upper respiratory tract infection by real-time RT-PCR assays. PLoS One 7: e38638. doi: 10.1371/journal.pone.0038638

41. Mackay IM,, Arden KE,, Speicher DJ,, O’Neil NT,, McErlean PK,, Greer RM,, Nissen MD,, Sloots TP. 2012. Co-circulation of four human coronaviruses (HCoVs) in Queensland children with acute respiratory tract illnesses in 2004. Viruses 4: 637– 653.

42. Prill MM,, Iwane MK,, Edwards KM,, Williams JV,, Weinberg GA,, Staat MA,, Willby MJ,, Talbot HK,, Hall CB,, Szilagyi PG,, Griffin MR,, Curns AT,, Erdman DD; New Vaccine Surveillance Network. 2012. Human coronavirus in young children hospitalized for acute respiratory illness and asymptomatic controls. Pediatr Infect Dis J 31: 235– 240.

43. Buecher C,, Mardy S,, Wang W,, Duong V,, Vong S,, Naughtin M,, Vabret A,, Freymuth F,, Deubel V,, Buchy P. 2010. Use of a multiplex PCR/RT-PCR approach to assess the viral causes of influenza-like illnesses in Cambodia during three consecutive dry seasons. J Med Virol 82: 1762– 1772.

44. Dijkman R,, Jebbink MF,, Gaunt E,, Rossen JW,, Templeton KE,, Kuijpers TW,, van der Hoek L. 2012. The dominance of human coronavirus OC43 and NL63 infections in infants. J Clin Virol 53: 135– 139.

45. Regamey N,, Kaiser L,, Roiha HL,, Deffernez C,, Kuehni CE,, Latzin P,, Aebi C,, Frey U, Swiss Paediatric Respiratory Research Group. 2008. Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study. Pediatr Infect Dis J 27: 100– 105.

46. Ren L,, Gonzalez R,, Xu J,, Xiao Y,, Li Y,, Zhou H,, Li J,, Yang Q,, Zhang J,, Chen L,, Wang W,, Vernet G,, Paranhos-Baccalà G,, Wang Z,, Wang J. 2011. Prevalence of human coronaviruses in adults with acute respiratory tract infections in Beijing, China. J Med Virol 83: 291– 297.

47. van der Zalm MM,, Uiterwaal CS,, Wilbrink B,, de Jong BM,, Verheij TJ,, Kimpen JL,, van der Ent CK. 2009. Respiratory pathogens in respiratory tract illnesses during the first year of life: a birth cohort study. Pediatr Infect Dis J 28: 472– 476.

48. Zlateva KT,, Coenjaerts FE,, Crusio KM,, Lammens C,, Leus F,, Viveen M,, Ieven M,, Spaan WJ,, Claas EC,, Gorbalenya AE. 2013. No novel coronaviruses identified in a large collection of human nasopharyngeal specimens using family-wide CODEHOP-based primers. Arch Virol 158: 251– 255.

49. Kaye HS,, Dowdle WR. 1975. Seroepidemiologic survey of coronavirus (strain 229E) infections in a population of children. Am J Epidemiol 101: 238– 244.

50. Kaye HS,, Marsh HB,, Dowdle WR. 1971. Seroepidemiologic survey of coronavirus (strain OC 43) related infections in a children’s population. Am J Epidemiol 94: 43– 49.

51. van der Hoek L,, Ihorst G,, Sure K,, Vabret A,, Dijkman R,, de Vries M,, Forster J,, Berkhout B,, Uberla K. 2010. Burden of disease due to human coronavirus NL63 infections and periodicity of infection. J Clin Virol 48: 104– 108.

52. Monto AS,, Lim SK. 1974. The Tecumseh study of respiratory illness. VI. Frequency of and relationship between outbreaks of coronavirus infection. J Infect Dis 129: 271– 276.

53. Schmidt OW,, Allan ID,, Cooney MK,, Foy HM,, Fox JP. 1986. Rises in titers of antibody to human coronaviruses OC43 and 229E in Seattle families during 1975-1979. Am J Epidemiol 123: 862– 868.

54. Callow KA,, Parry HF,, Sergeant M,, Tyrrell DA. 1990. The time course of the immune response to experimental coronavirus infection of man. Epidemiol Infect 105: 435– 446.

55. Dijkman R,, Jebbink MF,, El Idrissi NB,, Pyrc K,, Müller MA,, Kuijpers TW,, Zaaijer HL,, van der Hoek L. 2008. Human coronavirus NL63 and 229E seroconversion in children. J Clin Microbiol 46: 2368– 2373.

56. Shao X,, Guo X,, Esper F,, Weibel C,, Kahn JS. 2007. Seroepidemiology of group I human coronaviruses in children. J Clin Virol 40: 207– 213.

57. Gorse GJ,, Patel GB,, Vitale JN,, O’Connor TZ. 2010. Prevalence of antibodies to four human coronaviruses is lower in nasal secretions than in serum. Clin Vaccine Immunol 17: 1875– 1880.

58. Chan CM,, Tse H,, Wong SS,, Woo PC,, Lau SK,, Chen L,, Zheng BJ,, Huang JD,, Yuen KY. 2009. Examination of seroprevalence of coronavirus HKU1 infection with S protein-based ELISA and neutralization assay against viral spike pseudotyped virus. J Clin Virol 45: 54– 60.

59. Blanchard EG,, Miao C,, Haupt TE,, Anderson LJ,, Haynes LM. 2011. Development of a recombinant truncated nucleocapsid protein based immunoassay for detection of antibodies against human coronavirus OC43. J Virol Methods 177: 100– 106.

60. Hofmann H,, Pyrc K,, van der Hoek L,, Geier M,, Berkhout B,, Pohlmann S. 2005. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc Natl Acad Sci USA 102: 7988– 7993.

61. Milano F,, Campbell AP,, Guthrie KA,, Kuypers J,, Englund JA,, Corey L,, Boeckh M. 2010. Human rhinovirus and coronavirus detection among allogeneic hematopoietic stem cell transplantation recipients. Blood 115: 2088– 2094.

62. Resta S,, Luby JP,, Rosenfeld CR,, Siegel JD. 1985. Isolation and propagation of a human enteric coronavirus. Science 229: 978– 981.

63. Sizun J,, Yu MW,, Talbot PJ. 2000. Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source of hospital-acquired infections. J Hosp Infect 46: 55– 60.

64. Müller A,, Tillmann RL,, Müller A,, Simon A,, Schildgen O. 2008. Stability of human metapneumovirus and human coronavirus NL63 on medical instruments and in the patient environment. J Hosp Infect 69: 406– 408.

65. Ijaz MK,, Brunner AH,, Sattar SA,, Nair RC,, Johnson-Lussenburg CM. 1985. Survival characteristics of airborne human coronavirus 229E. J Gen Virol 66: 2743– 2748.

66. Birch CJ,, Clothier HJ,, Seccull A,, Tran T,, Catton MC,, Lambert SB,, Druce JD. 2005. Human coronavirus OC43 causes influenza-like illness in residents and staff of aged-care facilities in Melbourne, Australia. Epidemiol Infect 133: 273– 277.

67. Song HD,, Tu CC,, Zhang GW,, Wang SY,, Zheng K,, Lei LC,, Chen QX,, Gao YW,, Zhou HQ,, Xiang H,, Zheng HJ,, Chern SW,, Cheng F,, Pan CM,, Xuan H,, Chen SJ,, Luo HM,, Zhou DH,, Liu YF,, He JF,, Qin PZ,, Li LH,, Ren YQ,, Liang WJ,, Yu YD,, Anderson L,, Wang M,, Xu RH,, Wu XW,, Zheng HY,, Chen JD,, Liang G,, Gao Y,, Liao M,, Fang L,, Jiang LY,, Li H,, Chen F,, Di B,, He LJ,, Lin JY,, Tong S,, Kong X,, Du L,, Hao P,, Tang H,, Bernini A,, Yu XJ,, Spiga O,, Guo ZM,, Pan HY,, He WZ,, Manuguerra JC,, Fontanet A,, Danchin A,, Niccolai N,, Li YX,, Wu CI,, Zhao GP. 2005. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human. Proc Natl Acad Sci USA 102: 2430– 2435.

68. Cheng PK,, Wong DA,, Tong LK,, Ip SM,, Lo AC,, Lau CS,, Yeung EY,, Lim WW. 2004. Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome. Lancet 363: 1699– 1700.

69. Hijawi B,, Abdallat M,, Sayaydeh A,, Alqasrawi S,, Haddadin A,, Jaarour N,, Alsheikh S,, Alsanouri T. 2013. Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation. East Mediterr Health J 19: S12– S18.

70. Assiri A,, McGeer A,, Perl TM,, Price CS,, Al Rabeeah AA,, Cummings DA,, Alabdullatif ZN,, Assad M,, Almulhim A,, Makhdoom H,, Madani H,, Alhakeem R,, Al-Tawfiq JA,, Cotten M,, Watson SJ,, Kellam P,, Zumla AI,, Memish ZA; KSA MERS-CoV Investigation Team. 2013. Hospital outbreak of Middle East respiratory syndrome coronavirus. N Engl J Med 369: 407– 416.

71. Guery B,, Poissy J,, el Mansouf L,, Séjourné C,, Ettahar N,, Lemaire X,, Vuotto F,, Goffard A,, Behillil S,, Enouf V,, Caro V,, Mailles A,, Che D,, Manuguerra JC,, Mathieu D,, Fontanet A,, van der Werf S; MERS-CoV study group. 2013. Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission. Lancet 381: 2265– 2272.

72. Memish ZA,, Zumla AI,, Al-Hakeem RF,, Al-Rabeeah AA,, Stephens GM. 2013. Family cluster of Middle East respiratory syndrome coronavirus infections. N Engl J Med 369: 587.

73. Bradburne AF,, Bynoe ML,, Tyrrell DA. 1967. Effects of a “new” human respiratory virus in volunteers. Br Med J 3: 767– 769.

74. Bradburne AF,, Somerset BA. 1972. Coronative antibody tires in sera of healthy adults and experimentally infected volunteers. J Hyg (Lond) 70: 235– 244.

75. Sung JY,, Lee HJ,, Eun BW,, Kim SH,, Lee SY,, Lee JY,, Park KU,, Choi EH. 2010. Role of human coronavirus NL63 in hospitalized children with croup. Pediatr Infect Dis J 29: 822– 826.

76. van der Hoek L,, Sure K,, Ihorst G,, Stang A,, Pyrc K,, Jebbink MF,, Petersen G,, Forster J,, Berkhout B,, Uberla K. 2005. Croup is associated with the novel coronavirus NL63. PLoS Med 2: e240. (Republished Adv Exp Mol Biol 581:485–491, 2006.)

77. Wu PS,, Chang LY,, Berkhout B,, van der Hoek L,, Lu CY,, Kao CL,, Lee PI,, Shao PL,, Lee CY,, Huang FY,, Huang LM. 2008. Clinical manifestations of human coronavirus NL63 infection in children in Taiwan. Eur J Pediatr 167: 75– 80.

78. Singleton RJ,, Bulkow LR,, Miernyk K,, DeByle C,, Pruitt L,, Hummel KB,, Bruden D,, Englund JA,, Anderson LJ,, Lucher L,, Holman RC,, Hennessy TW. 2010. Viral respiratory infections in hospitalized and community control children in Alaska. J Med Virol 82: 1282– 1290.

79. Kuypers J,, Martin ET,, Heugel J,, Wright N,, Morrow R,, Englund JA. 2007. Clinical disease in children associated with newly described coronavirus subtypes. Pediatrics 119: e70– e76.

80. Templeton KE,, Scheltinga SA,, van den Eeden WC,, Graffelman AW,, van den Broek PJ,, Claas EC. 2005. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis 41: 345– 351.

81. Falsey AR,, Walsh EE,, Hayden FG. 2002. Rhinovirus and coronavirus infection-associated hospitalizations among older adults. J Infect Dis 185: 1338– 1341.

82. Bosis S,, Esposito S,, Niesters HG,, Zuccotti GV,, Marseglia G,, Lanari M,, Zuin G,, Pelucchi C,, Osterhaus AD,, Principi N. 2008. Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences. Clin Microbiol Infect 14: 677– 684.

83. Gaunt ER,, Harvala H,, McIntyre C,, Templeton KE,, Simmonds P. 2011. Disease burden of the most commonly detected respiratory viruses in hospitalized patients calculated using the disability adjusted life year (DALY) model. J Clin Virol 52: 215– 221.

84. Gerna G,, Passarani N,, Battaglia M,, Rondanelli EG. 1985. Human enteric coronaviruses: antigenic relatedness to human coronavirus OC43 and possible etiologic role in viral gastroenteritis. J Infect Dis 151: 796– 803.

85. Payne CM,, Ray CG,, Borduin V,, Minnich LL,, Lebowitz MD. 1986. An eight-year study of the viral agents of acute gastroenteritis in humans: ultrastructural observations and seasonal distribution with a major emphasis on coronavirus-like particles. Diagn Microbiol Infect Dis 5: 39– 54.

86. Esper F,, Ou Z,, Huang YT. 2010. Human coronaviruses are uncommon in patients with gastrointestinal illness. J Clin Virol 48: 131– 133.

87. Jevšnik M,, Steyer A,, Zrim T,, Pokorn M,, Mrvicˇ T,, Grosek Š,, Strle F,, Lusa L,, Petrovec M. 2013. Detection of human coronaviruses in simultaneously collected stool samples and nasopharyngeal swabs from hospitalized children with acute gastroenteritis. Virol J 10: 46.

88. Risku M,, Lappalainen S,, Rasanen S,, Vesikari T. 2010. Detection of human coronaviruses in children with acute gastroenteritis. J Clin Virol 48: 27– 30.

89. Arbour N,, Day R,, Newcombe J,, Talbot PJ. 2000. Neuroinvasion by human respiratory coronaviruses. J Virol 74: 8913– 8921.

90. Peiris JS,, Guan Y,, Yuen KY. 2004. Severe acute respiratory syndrome. Nat Med 10: S88– S97.

91. Assiri A,, Al-Tawfiq JA,, Al-Rabeeah AA,, Al-Rabiah FA,, Al-Hajjar S,, Al-Barrak A,, Flemban H,, Al-Nassir WN,, Balkhy HH,, Al-Hakeem RF,, Makhdoom HQ,, Zumla AI,, Memish ZA. 2013. Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: A descriptive study. Lancet Infect Dis 13: 752– 761.

92. Penttinen PM,, Kaasik-Aaslav K,, Friaux A,, Donachie A,, Sudre B,, Amato-Gauci AJ,, Memish ZA,, Coulombier D. 2013. Taking stock of the first 133 MERS coronavirus cases globally—is the epidemic changing? Euro Surveill 18: 20596.

93. Barnard DL,, Kumaki Y. 2011. Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy. Future Virol 6: 615– 631.

94. Stockman LJ,, Bellamy R,, Garner P. 2006. SARS: systematic review of treatment effects. PLoS Med 3: e343.

95. de Wilde AH,, Raj VS,, Oudshoorn D,, Bestebroer TM,, van Nieuwkoop S,, Limpens RW,, Posthuma CC,, van der Meer Y,, Bárcena M,, Haagmans BL,, Snijder EJ,, van den Hoogen BG. 2013. MERS-coronavirus replication induces severe in vitro cytopathology and is strongly inhibited by cyclosporin A or interferon-αtreatment. J Gen Virol 94: 1749– 1760.

96. Chan JF,, Chan KH,, Kao RY,, To KK,, Zheng BJ,, Li CP,, Li PT,, Dai J,, Mok FK,, Chen H,, Hayden FG,, Yuen KY. 2013. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect 67: 606– 616.

97. Falzarano D,, de Wit E,, Rasmussen AL,, Feldmann F,, Okumura A,, Scott DP,, Brining D,, Bushmaker T,, Martellaro C,, Baseler L,, Benecke AG,, Katze MG,, Munster VJ,, Feldmann H. 2013. Treatment with interferon-α2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med 19: 1313– 1317.

98. Fujimoto K,, Chan KH,, Takeda K,, Lo KF,, Leung RH,, Okamoto T. 2008. Sensitive and specific enzyme-linked immunosorbent assay using chemiluminescence for detection of severe acute respiratory syndrome viral infection. J Clin Microbiol 46: 302– 310.

99. Lau SK,, Woo PC,, Wong BH,, Tsoi HW,, Woo GK,, Poon RW,, Chan KH,, Wei WI,, Peiris JS,, Yuen KY. 2004. Detection of severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein in SARS patients by enzyme-linked immunosorbent assay. J Clin Microbiol 42: 2884– 2889.

100. Li YH,, Li J,, Liu XE,, Wang L,, Li T,, Zhou YH,, Zhuang H. 2005. Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: comparison with results of other viral markers. J Virol Methods 130: 45– 50.

101. Liu IJ,, Chen PJ,, Yeh SH,, Chiang YP,, Huang LM,, Chang MF,, Chen SY,, Yang PC,, Chang SC,, Wang WK; SARS Research Group of the National Taiwan University College of Medicine-National Taiwan University Hospital. 2005. Immunofluorescence assay for detection of the nucleocapsid antigen of the severe acute respiratory syndrome (SARS)-associated coronavirus in cells derived from throat wash samples of patients with SARS. J Clin Microbiol 43: 2444– 2448.

102. Sizun J,, Arbour N,, Talbot PJ. 1998. Comparison of immunofluorescence with monoclonal antibodies and RT-PCR for the detection of human coronaviruses 229E and OC43 in cell culture. J Virol Methods 72: 145– 152.

103. Sastre P,, Dijkman R,, Camuñas A,, Ruiz T,, Jebbink MF,, van der Hoek L,, Vela C,, Rueda P. 2011. Differentiation between human coronaviruses NL63 and 229E using a novel double-antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal antibodies. Clin Vaccine Immunol 18: 113– 118.

104. Gerna G,, Campanini G,, Rovida F,, Percivalle E,, Sarasini A,, Marchi A,, Baldanti F. 2006. Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients. J Med Virol 78: 938– 949.

105. Dare RK,, Fry AM,, Chittaganpitch M,, Sawanpanyalert P,, Olsen SJ,, Erdman DD. 2007. Human coronavirus infections in rural Thailand: a comprehensive study using real-time reverse-transcription polymerase chain reaction assays. J Infect Dis 196: 1321– 1328.

106. de Souza Luna LK,, Heiser V,, Regamey N,, Panning M,, Drexler JF,, Mulangu S,, Poon L,, Baumgarte S,, Haijema BJ,, Kaiser L,, Drosten C. 2007. Generic detection of coronaviruses and differentiation at the prototype strain level by reverse transcription-PCR and nonfluorescent low-density microarray. J Clin Microbiol 45: 1049– 1052.

107. Vijgen L,, Keyaerts E,, Moës E,, Maes P,, Duson G,, van Ranst M. 2005. Development of one-step, real-time, quantitative reverse transcriptase PCR assays for absolute quantitation of human coronaviruses OC43 and 229E. J Clin Microbiol 43: 5452– 5456.

108. van Elden LJ,, van Loon AM,, van Alphen F,, Hendriksen KA,, Hoepelman AI,, van Kraaij MG,, Oosterheert JJ,, Schipper P,, Schuurman R,, Nijhuis M. 2004. 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 189: 652– 657.

109. Pyrc K,, Milewska A,, Potempa J. 2011. Development of loop-mediated isothermal amplification assay for detection of human coronavirus-NL63. J Virol Methods 175: 133– 136.

110. Anderson TP,, Werno AM,, Barratt K,, Mahagamasekera P,, Murdoch DR,, Jennings LC. 2013. Comparison of four multiplex PCR assays for the detection of viral pathogens in respiratory specimens. J Virol Methods 191: 118– 121.

111. Gadsby NJ,, Hardie A,, Claas EC,, Templeton KE. 2010. Comparison of the Luminex Respiratory Virus Panel fast assay with in-house real-time PCR for respiratory viral infection diagnosis. J Clin Microbiol 48: 2213– 2216.

112. Loeffelholz MJ,, Pong DL,, Pyles RB,, Xiong Y,, Miller AL,, Bufton KK,, Chonmaitree T. 2011. Comparison of the FilmArray Respiratory Panel and Prodesse real-time PCR assays for detection of respiratory pathogens. J Clin Microbiol 49: 4083– 4088.

113. Sakthivel SK,, Whitaker B,, Lu X,, Oliveira DB,, Stockman LJ,, Kamili S,, Oberste MS,, Erdman DD. 2012. Comparison of fast-track diagnostics respiratory pathogens multiplex real-time RT-PCR assay with in-house singleplex assays for comprehensive detection of human respiratory viruses. J Virol Methods 185: 259– 266.

114. Poon LL,, Chan KH,, Wong OK,, Yam WC,, Yuen KY,, Guan Y,, Lo YM,, Peiris JS. 2003. Early diagnosis of SARS coronavirus infection by real time RT-PCR. J Clin Virol 28: 233– 238.

115. Poon LL,, Wong BW,, Chan KH,, Ng SS,, Yuen KY,, Guan Y,, Peiris JS. 2005. Evaluation of real-time reverse transcriptase PCR and real-time loop-mediated amplification assays for severe acute respiratory syndrome coronavirus detection. J Clin Microbiol 43: 3457– 3459.

116. Mahony JB,, Richardson S. 2005. Molecular diagnosis of severe acute respiratory syndrome: the state of the art. J Mol Diagn 7: 551– 559.

117. Yam WC,, Chan KH,, Chow KH,, Poon LL,, Lam HY,, Yuen KY,, Seto WH,, Peiris JS. 2005. Clinical evaluation of real-time PCR assays for rapid diagnosis of SARS coronavirus during outbreak and post-epidemic periods. J Clin Virol 33: 19– 24.

118. Vijgen L,, Moës E,, Keyaerts E,, Li S,, van Ranst M. 2008. A pancoronavirus RT-PCR assay for detection of all known coronaviruses. Methods Mol Biol 454: 3– 12.

119. Corman VM,, Eckerle I,, Bleicker T,, Zaki A,, Landt O,, Eschbach-Bludau M,, van Boheemen S,, Gopal R,, Ballhause M,, Bestebroer TM,, Muth D,, Müller MA,, Drexler JF,, Zambon M,, Osterhaus AD,, Fouchier RM,, Drosten C. 2012. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill 17: 20285.

120. Corman VM,, Müller MA,, Costabel U,, Timm J,, Binger T,, Meyer B,, Kreher P,, Lattwein E,, Eschbach-Bludau M,, Nitsche A,, Bleicker T,, Landt O,, Schweiger B,, Drexler JF,, Osterhaus AD,, Haagmans BL,, Dittmer U,, Bonin F,, Wolff T,, Drosten C. 2012. Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections. Euro Surveill 17: 20334.

121. World Health Organization. 2014. Laboratory Testing for Middle East Respiratory Syndrome Coronavirus: Interim Recommendations (revised). September 2014. http://www.who.int/csr/disease/coronavirus_infections/WHO_interim_recommendations_lab_detection_MERSCoV_092014.pdf?ua=1

122. Lu X,, Whitaker B,, Sakthivel SK,, Kamili S,, Rose LE,, Lowe L,, Mohareb E,, Elassal EM,, Al-Sanouri T,, Haddadin A,, Erdman DD. 2014. Real-time reverse transcription polymerase chain reaction assay panel for Middle East respiratory syndrome coronavirus. J Clin Microbiol 52: 67– 75.

123. Vabret A,, Mouthon F,, Mourez T,, Gouarin S,, Petitjean J,, Freymuth F. 2001. Direct diagnosis of human respiratory coronaviruses 229E and OC43 by the polymerase chain reaction. J Virol Methods 97: 59– 66.

124. Herzog P,, Drosten C,, Muller MA. 2008. Plaque assay for human coronavirus NL63 using human colon carcinoma cells. Virol J 5: 138.

125. Schildgen O,, Jebbink MF,, de Vries M,, Pyrc K,, Dijkman R,, Simon A,, Müller A,, Kupfer B,, van der Hoek L. 2006. Identification of cell lines permissive for human coronavirus NL63. J Virol Methods 138: 207– 210.

126. Freymuth F,, Vabret A,, Rozenberg F,, Dina J,, Petitjean J,, Gouarin S,, Legrand L,, Corbet S,, Brouard J,, Lebon P. 2005. Replication of respiratory viruses, particularly influenza virus, rhinovirus, and coronavirus in HuH7 hepatocarcinoma cell line. J Med Virol 77: 295– 301.

127. Dijkman R,, Jebbink MF,, Koekkoek SM,, Deijs M,, Jónsdóttir HR,, Molenkamp R,, Ieven M,, Goossens H,, Thiel V,, van der Hoek L. 2013. Isolation and characterization of current human coronavirus strains in primary human epithelial cell cultures reveal differences in target cell tropism. J Virol 87: 6081– 6090.

128. Pyrc K,, Sims AC,, Dijkman R,, Jebbink M,, Long C,, Deming D,, Donaldson E,, Vabret A,, Baric R,, van der Hoek L,, Pickles R. 2010. Culturing the unculturable: human coronavirus HKU1 infects, replicates, and produces progeny virions in human ciliated airway epithelial cell cultures. J Virol 84: 11255– 11263.

129. Kaye M. 2006. SARS-associated coronavirus replication in cell lines. Emerg Infect Dis 12: 128– 133.

130. Lehmann C,, Wolf H,, Xu J,, Zhao Q,, Shao Y,, Motz M,, Lindner P. 2008. A line immunoassay utilizing recombinant nucleocapsid proteins for detection of antibodies to human coronaviruses. Diagn Microbiol Infect Dis 61: 40– 48.

131. Liang FY,, Lin LC,, Ying TH,, Yao CW,, Tang TK,, Chen YW,, Hou MH. 2013. Immunoreactivity characterisation of the three structural regions of the human coronavirus OC43 nucleocapsid protein by Western blot: implications for the diagnosis of coronavirus infection. J Virol Methods 187: 413– 420.

132. Buchholz U,, Müller MA,, Nitsche A,, Sanewski A,, Wevering N,, Bauer-Balci T,, Bonin F,, Drosten C,, Schweiger B,, Wolff T,, Muth D,, Meyer B,, Buda S,, Krause G,, Schaade L,, Haas W. 2013. Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012. Euro Surveill 18: 20406.

133. Reusken C,, Mou H,, Godeke GJ,, van der Hoek L,, Meyer B,, Müller MA,, Haagmans B,, de Sousa R,, Schuurman N,, Dittmer U,, Rottier P,, Osterhaus A,, Drosten C,, Bosch BJ,, Koopmans M. 2013. Specific serology for emerging human coronaviruses by protein microarray. Euro Surveill 18: 20441.

134. Saunders N,, Zambon M,, Sharp I,, Siddiqui R,, Bermingham A,, Ellis J,, Vipond B,, Sails A,, Moran-Gilad J,, Marsh P,, Guiver M, HPA Microbiology Services Division. 2013. Guidance on the development and validation of diagnostic tests that depend on nucleic acid amplification and detection. J Clin Virol 56: 260– 270.

135. Clinical and Laboratory Standards Institute. 2006. Molecular Diagnostic Methods for Infectious Diseases; Approved Guideline - Second Edition. CLSI document MM03-A2. Clinical and Laboratory Standards Institute, Wayne, PA.

136. Loens K,, van Loon AM,, Coenjaerts F,, van Aarle Y,, Goossens H,, Wallace P,, Claas EJ,, Ieven M, GRACE Study Group. 2012. Performance of different mono- and multiplex nucleic acid amplification tests on a multipathogen external quality assessment panel. J Clin Microbiol 50: 977– 987.

137. Templeton KE,, Forde CB,, Loon AM,, Claas EC,, Niesters HG,, Wallace P,, Carman WF. 2006. A multi-centre pilot proficiency programme to assess the quality of molecular detection of respiratory viruses. J Clin Virol 35: 51– 58.

138. Public Health England. 2013. Good Laboratory Practice when Performing Molecular Amplification Assays. UK Standards for Microbiology Investigations. Q4, issue 4.4. http://www.hpa.org.uk/SMI/pdf

139. Palm D,, Pereyaslov D,, Vaz J,, Broberg E,, Zeller H,, Gross D,, Brown CS,, Struelens MJ; Joint ECDC-WHO Regional Office for Europe Novel Coronavirus Laboratory Survey Participants; ECDC National Microbiology Focal Points; WHO European Region EuroFlu Network; European Network for Diagnostics of “Imported” Viral Diseases (ENIVD). 2012. Laboratory capability for molecular detection and confirmation of novel coronavirus in Europe, November 2012. Euro Surveill 17: 20335.

140. Esposito S,, Bosis S,, Niesters HG,, Tremolati E,, Begliatti E,, Rognoni A,, Tagliabue C,, Principi N,, Osterhaus AD. 2006. Impact of human coronavirus infections in otherwise healthy children who attended an emergency department. J Med Virol 78: 1609– 1615.

141. Centers for Disease Control and Prevention. 2014. Interim Laboratory Biosafety Guidelines for Handling and Processing Specimens Associated with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Version 2 May 29, 2014. http://www.cdc.gov/coronavirus/mers/guidelines-lab-biosafety.html#packing

Tables

Coronaviruses*

/content/10.1128/9781555817381.mcm11.ch90.ch90.tab001

TABLE 1

Examples of published real-time RT-PCR assays for the detection of endemic HCoVs using different target genes a

TABLE 1

Examples of published real-time RT-PCR assays for the detection of endemic HCoVs using different target genes a

/content/10.1128/9781555817381.mcm11.ch90.ch90.tab002

TABLE 2

Examples of currently available commercial assays incorporating the detection of endemic HCoVs a

TABLE 2

Examples of currently available commercial assays incorporating the detection of endemic HCoVs a