Human coronavirus NL63

Comparison of the genome organization of coronaviruses infecting humans[1]
Specialty| Infectious disease

Human coronavirus NL63 (HCoV-NL63) is a species of coronavirus, specifically a Setracovirus from among the Alphacoronavirus genus. It was identified in late 2004 in patients in the Netherlands by Lia van der Hoek and Krzysztof Pyrc[2] using a novel virus discovery method VIDISCA.[3] Later on the discovery was confirmed by the researchers from the Rotterdam, the Netherlands [4] The virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to ACE2.[5][6][7] Infection with the virus has been confirmed worldwide, and has an association with many common symptoms and diseases. Associated diseases include mild to moderate upper respiratory tract infections, severe lower respiratory tract infection, croup and bronchiolitis.[8][9][1]

The virus is found primarily in young children, the elderly, and immunocompromised patients with acute respiratory illness. It also has a seasonal association in temperate climates. A study performed in Amsterdam estimated the presence of HCoV-NL63 in approximately 4.7% of common respiratory illnesses.[10] The natural reservoirs are palm civets and bats.[11] Estimates of its divergence from another coronavirus (HCoV-229E) are around 1000 years ago; it has likely circulated in humans for centuries.[12]

The evolution of HCoV-NL63 appears to have involved recombination between an ancestral NL63-like virus circulating in African Triaenops afer bats and a CoV 229E-like virus circulating in Hipposideros bats.[13] Recombinant viruses can arise when two viral genomes are present in the same host cell.

## Contents

* 1 Symptoms and signs
* 2 Cause
* 3 Transmission
* 4 Virology
* 5 Diagnosis
* 6 Prevention
* 7 Treatment
* 8 Research
* 9 References
* 10 External links

## Symptoms and signs[edit | edit source]

The first cases of the infection with HCoV-NL63 were found in young children with severe lower respiratory tract infections admitted to hospitals. While the clinical presentation of the virus can be severe, it has also been found in mild cases of respiratory infection. The comorbidity of HCoV-NL63 with other respiratory infections, has made the specific symptoms of the virus difficult to pinpoint. A study of clinical symptoms in HCoV-NL63 patients without secondary infection, reported the most common symptoms to be fever, cough, rhinitis, sore throat, hoarseness, bronchitis, bronchiolitis, pneumonia, and croup.[9] An early study investigating children with lower respiratory tract illness, found that HCoV-NL63 was more commonly found in outpatients than hospitalized patients, suggesting that it is a common cold virus similar to HCoV-229E and HCoV-OC43, which generally cause less severe symptoms.[14] However, the high frequency of croup is specific to HCoV-NL63 infection.

## Cause[edit | edit source]

Seasonal distribution of HCoV-NL63 shows a preferential detection in the period between November and March

Human coronavirus NL63

Transmission electron micrograph of HCoV-NL63
Virus classification
(unranked):  | Virus
Realm:  | Riboviria
Kingdom:  | Orthornavirae
Phylum:  | Pisuviricota
Class:  | Pisoniviricetes
Order:  | Nidovirales
Family:  | Coronaviridae
Genus:  | Alphacoronavirus
Subgenus:  | Setracovirus
Species:  |

Human coronavirus NL63

It is believed that the route of HCoV-NL63 spread is through direct person-to-person transmission in highly populated areas. The virus can survive for up to a week outside of the body in aqueous solutions at room temperature and three hours on dry surfaces.[15][16] Most people will be infected with a coronavirus in their lifetime, but some populations are more susceptible to HCoV-NL63. These populations include children under the age of 5, the elderly, and immunocompromised individuals. The virus seems to have seasonal incidence, occurring most frequently in the winter months in temperate climates. In more extreme and tropical climates the virus has no preference toward a particular season. Many studies have reported the co-occurrence of HCoV-NL63 with other human coronavirus, Influenza A virus, Human orthopneumovirus (RSV), parainfluenza virus, and Human metapneumovirus (hMPV).[17][1]

## Transmission[edit | edit source]

As HCoV-NL63 infects the respiratory tract it must be inhaled to get there, and is therefore transmitted by the airborne route. The virus is able to survive for up to seven days in respiratory secretions and remains infectious at room temperature. Once the virus has entered the host, it binds to cellular receptors via its spike proteins. The virus is able to use Angiotensin-converting enzyme 2 (ACE2) as an entry receptor to bind to and enter target cells.[18]

## Virology[edit | edit source]

HCoV-NL63 is one of seven known coronaviruses to infect humans. The other six are:[19]

* Human coronavirus 229E (HCoV-229E)
* Human coronavirus OC43 (HCoV-OC43)
* Human coronavirus HKU1 (HCoV-HKU1)
* Middle East respiratory syndrome-related coronavirus (MERS-CoV)
* Severe acute respiratory syndrome coronavirus (SARS-CoV-1)
* Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

## Diagnosis[edit | edit source]

It is difficult to distinguish between symptoms caused by infection of the HCoV-NL63 virus and those caused by other common human viruses, making diagnosis and detection complex. Reverse transcription polymerase chain reaction of samples collected through nasopharyngeal swab is the most commonly used method for detection of the virus.[1] Viral culture or blood serum testing for antibodies may also be used for the confirmation of infection.

## Prevention[edit | edit source]

The United States Centers for Disease Control and Prevention (CDC) recommends several measures for the prevention of infection with HCoV-NL63 including: washing hands often with soap and water, avoiding close contact with sick individuals, and not touching the eyes, mouth, or nose.[20]

## Treatment[edit | edit source]

Treatment for the HCoV-NL63 virus is dependent on the severity of associated symptomology. Most mild to moderate infections will go away on their own. Symptoms can be relieved by taking a pain reliever or fever medication, taking a hot shower, or using a humidifier. Antiviral treatment may be necessary for infected patients that end up in the intensive care unit (ICU) due to acute respiratory infection. Intravenous immunoglobulin is an FDA approved HCoV-NL63 inhibitor that is also used to treat primary immune deficiency, RSV, and Kawasaki disease.[10]

## Research[edit | edit source]

Research published in 2005 by Esper, et al. suggested an association of HCoV-NL63 infection with Kawasaki disease, a systemic vasculitis in childhood that may result in aneurysms of the coronary arteries.[21] In the developed world, Kawasaki disease is the most common cause of acquired heart disease in children.[22] Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because of recent evidence that this virus uses the same cellular receptor (ACE2) as both SARS-CoV (the causal agent of SARS) and SARS-CoV-2 (the causal agent of COVID-19),[18] the latter of which provokes an eerily similar immune response. HCoV-NL63 has also been found in the intestinal tract of infected individuals and linked to gastroenteritis.[23] This type of infection is the direct result of the viral invasion of the mucosal lining of the intestines. The role of HCoV-NL63 in gastroenteritis is unclear due to typical coinfection with other viruses in this condition. HCoV-NL63 is likely under-detected due its role in many mild to moderate respiratory infections and comorbidity with other disease. Researchers have suggested that more comprehensive, population-based studies are necessary to determine the effects of this virus on systems outside of the respiratory tract.

## References[edit | edit source]

1. ↑ 1.0 1.1 1.2 1.3 Abdul-Rasool S, Fielding BC (May 2010). "Understanding Human Coronavirus HCoV-NL63". The Open Virology Journal. 4: 76–84. doi:10.2174/1874357901004010076. PMC 2918871. PMID 20700397.
2. ↑ van der Hoek, Lia; Pyrc, Krzysztof; Jebbink, Maarten F.; Vermeulen-Oost, Wilma; Berkhout, Ron J. M.; Wolthers, Katja C.; Wertheim-van Dillen, Pauline M. E.; Kaandorp, Jos; Spaargaren, Joke; Berkhout, Ben (April 2004). "Identification of a new human coronavirus". Nature Medicine. 10 (4): 368–373. doi:10.1038/nm1024. ISSN 1546-170X. PMC 7095789. PMID 15034574.
3. ↑ Pyrc, Krzysztof; Jebbink, Maarten F.; Berkhout, Ben; van der Hoek, Lia (2008), Cavanagh, Dave (ed.), "Detection of New Viruses by VIDISCA: Virus Discovery Based on cDNA-Amplified Fragment Length Polymorphism", SARS- and Other Coronaviruses: Laboratory Protocols, Methods in Molecular Biology, Totowa, NJ: Humana Press, vol. 454, pp. 73–89, doi:10.1007/978-1-59745-181-9_7, ISBN 978-1-59745-181-9, PMC 7121709, PMID 19057862, archived from the original on 2024-01-17, retrieved 2023-06-09
4. ↑ Fouchier RA, Hartwig NG, Bestebroer TM, Niemeyer B, de Jong JC, Simon JH, Osterhaus AD (Apr 2004). "A previously undescribed coronavirus associated with respiratory disease in humans". Proc Natl Acad Sci USA. 101 (16): 6212–6216. Bibcode:2004PNAS..101.6212F. doi:10.1073/pnas.0400762101. PMC 395948. PMID 15073334.
5. ↑ Hofmann, Heike; Pyrc, Krzysztof; van der Hoek, Lia; Geier, Martina; Berkhout, Ben; Pöhlmann, Stefan (2005-05-31). "Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry". Proceedings of the National Academy of Sciences. 102 (22): 7988–7993. Bibcode:2005PNAS..102.7988H. doi:10.1073/pnas.0409465102. ISSN 0027-8424. PMC 1142358. PMID 15897467.
6. ↑ "ACE2 angiotensin I converting enzyme 2 - Gene". NCBI. 2020-02-28. Archived from the original on 2014-12-24. Retrieved 2020-03-21. "The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. The organ- and cell-specific expression of this gene suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2 (COVID-19 virus)."
7. ↑ Fehr AR, Perlman S (2015). "Coronaviruses: An Overview of Their Replication and Pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. Vol. 1282\. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC 4369385. PMID 25720466.
8. ↑ Lia van der Hoek, Krzysztof Pyrc, Ben Berkhout. "Human coronavirus NL63, a new respiratory virus". academic.oup.com. Archived from the original on 2023-06-09. Retrieved 2023-06-09.`{{cite web}}`: CS1 maint: multiple names: authors list (link)
9. ↑ 9.0 9.1 Hoek, Lia van der; Sure, Klaus; Ihorst, Gabriele; Stang, Alexander; Pyrc, Krzysztof; Jebbink, Maarten F.; Petersen, Gudula; Forster, Johannes; Berkhout, Ben; Überla, Klaus (2005-08-23). "Croup Is Associated with the Novel Coronavirus NL63". PLOS Medicine. 2 (8): e240. doi:10.1371/journal.pmed.0020240. ISSN 1549-1676. PMC 1188248. PMID 16104827.
10. ↑ 10.0 10.1 van der Hoek L, Pyrc K, Berkhout B (September 2006). "Human coronavirus NL63, a new respiratory virus". FEMS Microbiology Reviews. 30 (5): 760–73. doi:10.1111/j.1574-6976.2006.00032.x. PMC 7109777. PMID 16911043.
11. ↑ Lim, Yvonne Xinyi; Ng, Yan Ling; Tam, James P.; Liu, Ding Xiang (2016-07-25). "Human Coronaviruses: A Review of Virus–Host Interactions". Diseases. 4 (3): 26. doi:10.3390/diseases4030026. ISSN 2079-9721. PMC 5456285. PMID 28933406. "See Table 1."
12. ↑ Pyrc, K (2006). "Mosaic structure of human coronavirus NL63, one thousand years of evolution". J. Mol. Biol. 364 (5): 964–973. doi:10.1016/j.jmb.2006.09.074. ISSN 0022-2836. PMC 7094706. PMID 17054987.
13. ↑ Tao, Y.; Shi, M.; Chommanard, C.; Queen, K.; Zhang, J.; Markotter, W.; Kuzmin, I. V.; Holmes, E. C.; Tong, S. (2017). "Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History". Journal of Virology. 91 (5). doi:10.1128/JVI.01953-16. PMC 5309958. PMID 28077633.
14. ↑ van der Hoek L, Berkhout B (July 2005). "Questions concerning the New Haven coronavirus". The Journal of Infectious Diseases. 192 (2): 350–1, author reply 353–4. doi:10.1086/430795. PMC 7110114. PMID 15962232.
15. ↑ Florek, Dominik; Burmistrz, Michal; Potempa, Jan; Pyrc, Krzysztof (2014-09-01). "Stability of infectious human coronavirus NL63". Journal of Virological Methods. 205: 87–90. doi:10.1016/j.jviromet.2014.04.001. ISSN 0166-0934. PMC 7113654. PMID 24747590.
16. ↑ "Human Coronavirus". Public Health Agency of Canada. 2011-08-19. Archived from the original on 2017-07-03. Retrieved July 22, 2015.
17. ↑ Golda, Anna; Malek, Natalia; Dudek, Bartosz; Zeglen, Slawomir; Wojarski, Jacek; Ochman, Marek; Kucewicz, Ewa; Zembala, Marian; Potempa, Jan; Pyrc, Krzysztof (2011). "Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells". Journal of General Virology. 92 (6): 1358–1368. doi:10.1099/vir.0.028381-0. ISSN 1465-2099. PMC 3168281. PMID 21325482.
18. ↑ 18.0 18.1 Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pöhlmann S (May 2005). "Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry". Proceedings of the National Academy of Sciences of the United States of America. 102 (22): 7988–93. Bibcode:2005PNAS..102.7988H. doi:10.1073/pnas.0409465102. PMC 1142358. PMID 15897467.
19. ↑ Leung, Daniel (20 January 2019). "Coronaviruses (including SARS)". Infectious Disease Advisor. Decision Support in Medicine, LLC. Archived from the original on 16 April 2021. Retrieved 1 August 2020.
20. ↑ "About Coronavirus". Center for Disease Control. Archived from the original on July 27, 2015. Retrieved July 22, 2015.
21. ↑ Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JS (February 2005). "Association between a novel human coronavirus and Kawasaki disease". J Infect Dis. 191 (4): 499–502. doi:10.1086/428291. PMC 7199489. PMID 15655771.
22. ↑ "Kawasaki Disease". Mayo Clinic. Archived from the original on August 13, 2015. Retrieved July 22, 2015.
23. ↑ Fielding BC (February 2011). "Human coronavirus NL63: a clinically important virus?". Future Microbiology. 6 (2): 153–9. doi:10.2217/fmb.10.166. PMC 7079714. PMID 21366416.

## External links[edit | edit source]

* Data related to Human coronavirus NL63 at Wikispecies

* v
* t
* e

Taxonomy of the Coronaviridae

Higher taxonomy: Riboviria > Orthornavirae > Pisuviricota > Pisoniviricetes > Nidovirales > Cornidovirineae > Coronaviridae

Orthocoronavirinae

Alphacoronavirus|

| Colacovirus|

* Bat coronavirus CDPHE15

Decacovirus|

* Bat coronavirus HKU10
* Rhinolophus ferrumequinum alphacoronavirus HuB-2013

Duvinacovirus|

* Human coronavirus 229E

Luchacovirus|

* Lucheng Rn rat coronavirus

Minacovirus|

* Mink coronavirus 1

Minunacovirus|

* Miniopterus bat coronavirus 1
* Miniopterus bat coronavirus HKU8

Myotacovirus|

* Myotis ricketti alphacoronavirus Sax-2011

Nyctacovirus|

* Nyctalus velutinus alphacoronavirus SC-2013
* Pipistrellus kuhlii coronavirus 3398

Pedacovirus|

* Porcine epidemic diarrhea virus
* Scotophilus bat coronavirus 512

Rhinacovirus|

* Rhinolophus bat coronavirus HKU2

Setracovirus|

* Human coronavirus NL63
* NL63-related bat coronavirus strain BtKYNL63-9b

Soracovirus|

* Sorex araneus coronavirus T14

Sunacovirus|

* Suncus murinus coronavirus X74

Tegacovirus|

* Alphacoronavirus 1
* Feline coronavirus
* Canine coronavirus
* Canine coronavirus HuPn-2018
* Transmissible gastroenteritis virus

Betacoronavirus|

| Embecovirus|

* Betacoronavirus 1
* Bovine coronavirus
* Human coronavirus OC43
* China Rattus coronavirus HKU24
* Human coronavirus HKU1
* Murine coronavirus
* Rat coronavirus
* Myodes coronavirus 2JL14

Hibecovirus|

* Bat Hp-betacoronavirus Zhejiang2013

Merbecovirus|

* Hedgehog coronavirus 1
* Middle East respiratory syndrome-related coronavirus
* London1_novel CoV/2012
* MERS coronavirus EMC/2012
* Pipistrellus bat coronavirus HKU5
* Tylonycteris bat coronavirus HKU4

Nobecovirus|

* Eidolon bat coronavirus C704
* Rousettus bat coronavirus GCCDC1
* Rousettus bat coronavirus HKU9

Sarbecovirus|

* SARS-related coronavirus
* SARS-CoV-1
* SARS-CoV-2
* Variants
* BANAL-52
* Bat SARS-like coronavirus WIV1
* RacCS203
* RaTG13
* RmYN02
* RpYN06
* SHC014-CoV

Gammacoronavirus|

| Brangacovirus|

* Goose coronavirus CB17

Cegacovirus|

* Beluga whale coronavirus SW1

Igacovirus|

* Avian coronavirus
* Avian coronavirus 9203
* Duck coronavirus 2714

Deltacoronavirus|

| Andecovirus|

* Wigeon coronavirus HKU20

Buldecovirus|

* Bulbul coronavirus HKU11
* Common moorhen coronavirus HKU21
* Coronavirus HKU15
* Munia coronavirus HKU13
* White-eye coronavirus HKU16

Herdecovirus|

* Night heron coronavirus HKU19

Letovirinae

| Alphaletovirus|

| Milecovirus|

* Microhyla letovirus 1

Source: ICTV ––  Wikispecies
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