View source for Human coronavirus NL63

{{short description|Species of virus}}
{{Virusbox
| image = 12985 2013 2210 MOESM6 ESM E.tif
| image_alt = 
| image_caption = [[Transmission electron micrograph]] of HCoV-NL63
| parent = Setracovirus
| species = Alphacoronavirus amsterdamense
| synonyms = * Human coronavirus NL63
* HCoV-NL63
| synonyms_ref = 
}}

'''''Alphacoronavirus amsterdamense''''' <ref>{{Cite web |title=Taxon Details {{!}} ICTV |url=https://ictv.global/taxonomy/taxondetails?taxnode_id=202301853&taxon_name=Alphacoronavirus%20amsterdamense |access-date=25 July 2024 |website=International Committee on Taxonomy of Viruses (ICTV)}}</ref>( also called '''''Human coronavirus NL63''''' abbreviated '''''HCoV-NL63''')'' is a species of [[coronavirus]], specifically a [[Setracovirus]] from among the [[Alphacoronavirus]] genus. It was identified in late 2004 in patients in [[Netherlands|the Netherlands]] by Lia van der Hoek and Krzysztof Pyrc<ref>{{Cite journal |last1=van der Hoek |first1=Lia |last2=Pyrc |first2=Krzysztof |last3=Jebbink |first3=Maarten F. |last4=Vermeulen-Oost |first4=Wilma |last5=Berkhout |first5=Ron J. M. |last6=Wolthers |first6=Katja C. |last7=Wertheim-van Dillen |first7=Pauline M. E. |last8=Kaandorp |first8=Jos |last9=Spaargaren |first9=Joke |last10=Berkhout |first10=Ben |date=April 2004 |title=Identification of a new human coronavirus |journal=Nature Medicine |language=en |volume=10 |issue=4 |pages=368–373 |doi=10.1038/nm1024 |pmid=15034574 |pmc=7095789 |issn=1546-170X}}</ref> using a novel virus discovery method VIDISCA.<ref>{{Citation |last1=Pyrc |first1=Krzysztof |date=2008 |url=https://doi.org/10.1007/978-1-59745-181-9_7 |work=SARS- and Other Coronaviruses: Laboratory Protocols |pages=73–89 |editor-last=Cavanagh |editor-first=Dave |access-date=2023-06-09 |series=Methods in Molecular Biology |place=Totowa, NJ |publisher=Humana Press |language=en |doi=10.1007/978-1-59745-181-9_7 |isbn=978-1-59745-181-9 |pmc=7121709 |pmid=19057862 |last2=Jebbink |first2=Maarten F. |last3=Berkhout |first3=Ben |last4=van der Hoek |first4=Lia|title=Detection of New Viruses by VIDISCA: Virus Discovery Based on cDNA-Amplified Fragment Length Polymorphism |volume=454 }}</ref> Later on the discovery was confirmed by the researchers from [[Rotterdam]].<ref name="Fouchier_2004">{{cite journal | vauthors = Fouchier RA, Hartwig NG, Bestebroer TM, Niemeyer B, de Jong JC, Simon JH, Osterhaus AD | title = A previously undescribed coronavirus associated with respiratory disease in humans | journal = Proc Natl Acad Sci USA | volume = 101 | pages = 6212–6216 | date = Apr 2004 | issue = 16 | pmid = 15073334 | pmc = 395948 | doi = 10.1073/pnas.0400762101 | bibcode = 2004PNAS..101.6212F | doi-access = free }}</ref> The virus is an [[Viral envelope|enveloped]], [[Sense (molecular biology)|positive-sense]], [[RNA|single-stranded]] [[RNA virus]] which enters its host cell by binding to [[ACE2]].<ref>{{Cite journal |last1=Hofmann |first1=Heike |last2=Pyrc |first2=Krzysztof |last3=van der Hoek |first3=Lia |last4=Geier |first4=Martina |last5=Berkhout |first5=Ben |last6=Pöhlmann |first6=Stefan |date=2005-05-31 |title=Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry |journal=Proceedings of the National Academy of Sciences |language=en |volume=102 |issue=22 |pages=7988–7993 |doi=10.1073/pnas.0409465102 |issn=0027-8424 |pmc=1142358 |pmid=15897467 |bibcode=2005PNAS..102.7988H |doi-access=free }}</ref><ref name="NCBI 2020">{{cite web | title=ACE2 angiotensin I converting enzyme 2 - Gene | website=NCBI | date=2020-02-28 | url=https://www.ncbi.nlm.nih.gov/gene/59272 | access-date=2020-03-21 | quote=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).}}</ref><ref>{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | series = Methods in Molecular Biology | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | isbn = 978-1-4939-2438-7 | veditors = Maier HJ, Bickerton E, Britton P | publisher = Springer }}</ref> 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 infection]]s, severe [[lower respiratory tract infection]], [[croup]] and bronchiolitis.<ref>{{Cite web |last=Lia van der Hoek, Krzysztof Pyrc, Ben Berkhout |title=Human coronavirus NL63, a new respiratory virus |url=https://academic.oup.com/femsre/article/30/5/760/2399118 |access-date=2023-06-09 |website=academic.oup.com}}</ref><ref name=":0">{{Cite journal |last1=Hoek |first1=Lia van der |last2=Sure |first2=Klaus |last3=Ihorst |first3=Gabriele |last4=Stang |first4=Alexander |last5=Pyrc |first5=Krzysztof |last6=Jebbink |first6=Maarten F. |last7=Petersen |first7=Gudula |last8=Forster |first8=Johannes |last9=Berkhout |first9=Ben |last10=Überla |first10=Klaus |date=2005-08-23 |title=Croup Is Associated with the Novel Coronavirus NL63 |journal=PLOS Medicine |language=en |volume=2 |issue=8 |pages=e240 |doi=10.1371/journal.pmed.0020240 |issn=1549-1676 |pmc=1188248 |pmid=16104827 |doi-access=free }}</ref><ref name="Abdul-Rasool_2010">{{cite journal | vauthors = Abdul-Rasool S, Fielding BC | title = Understanding Human Coronavirus HCoV-NL63 | journal = The Open Virology Journal | volume = 4 | pages = 76–84 | date = May 2010 | pmid = 20700397 | pmc = 2918871 | doi =  10.2174/1874357901004010076  |doi-access=free}}</ref>

The virus is found primarily in young children, the elderly, and [[immunodeficiency|immunocompromised]] patients with acute respiratory illness. It also has a seasonal association in [[temperate climate]]s. A study performed in Amsterdam estimated the presence of HCoV-NL63 in approximately 4.7% of common respiratory illnesses.<ref name="van_der_Hoek_2006">{{cite journal | vauthors = van der Hoek L, Pyrc K, Berkhout B | title = Human coronavirus NL63, a new respiratory virus | journal = FEMS Microbiology Reviews | volume = 30 | issue = 5 | pages = 760–73 | date = September 2006 | pmid = 16911043 | doi = 10.1111/j.1574-6976.2006.00032.x | pmc = 7109777 | doi-access = free }}</ref> The natural reservoirs are [[Paradoxurus|palm civets]] and bats.<ref>{{Cite journal|last1=Lim|first1=Yvonne Xinyi|last2=Ng|first2=Yan Ling|last3=Tam|first3=James P.|last4=Liu|first4=Ding Xiang|date=2016-07-25|title=Human Coronaviruses: A Review of Virus–Host Interactions|journal=Diseases|volume=4|issue=3|pages=26|doi=10.3390/diseases4030026|issn=2079-9721|pmc=5456285|pmid=28933406|quote=See Table 1.|doi-access=free}}</ref> Estimates of its divergence from another coronavirus ([[HCoV-229E]]) are around 1000 years ago; it has likely circulated in humans for centuries.<ref>{{Cite journal|last=Pyrc|first=K|date=2006|title=Mosaic structure of human coronavirus NL63, one thousand years of evolution.|journal=J. Mol. Biol.|volume=364|issue=5|pages=964–973|doi=10.1016/j.jmb.2006.09.074|pmid=17054987|pmc=7094706|issn=0022-2836}}</ref>

The evolution of HCoV-NL63 appears to have involved [[genetic recombination|recombination]] between an ancestral NL63-like virus circulating in [[African trident bat|African ''Triaenops afer'' bats]] and a [[Human coronavirus 229E|CoV 229E]]-like virus circulating in ''[[Hipposideros]]'' bats.<ref>{{cite journal | pmid = 28077633 | year = 2017 | last1 = Tao | first1 = Y. | last2 = Shi | first2 = M. | last3 = Chommanard | first3 = C. | last4 = Queen | first4 = K. | last5 = Zhang | first5 = J. | last6 = Markotter | first6 = W. | last7 = Kuzmin | first7 = I. V. | last8 = Holmes | first8 = E. C. | last9 = Tong | first9 = S. | title = Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History | journal = Journal of Virology | volume = 91 | issue = 5 | doi = 10.1128/JVI.01953-16 | pmc = 5309958 }}</ref> Recombinant viruses can arise when two viral [[genome]]s are present in the same host cell.

==Symptoms==
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]].<ref name=":0" /> 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 [[Human coronavirus 229E|HCoV-229E]] and [[Human coronavirus OC43|HCoV-OC43]], which generally cause less severe symptoms.<ref name="van_der_Hoek_2005">{{cite journal | vauthors = van der Hoek L, Berkhout B | title = Questions concerning the New Haven coronavirus | journal = The Journal of Infectious Diseases | volume = 192 | issue = 2 | pages = 350–1; author reply 353–4 | date = July 2005 | pmid = 15962232 | doi = 10.1086/430795 | pmc = 7110114 | doi-access = free }}</ref> However, the high frequency of [[croup]] is specific to HCoV-NL63 infection.

==Cause==
[[File:Journal.pmed.0020240.g001.tif|thumb|Seasonal distribution of HCoV-NL63 shows a preferential detection in the period between November and March]]

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 solution]]s at room temperature and three hours on dry surfaces.<ref>{{Cite journal |last1=Florek |first1=Dominik |last2=Burmistrz |first2=Michal |last3=Potempa |first3=Jan |last4=Pyrc |first4=Krzysztof |date=2014-09-01 |title=Stability of infectious human coronavirus NL63 |journal=Journal of Virological Methods |language=en |volume=205 |pages=87–90 |doi=10.1016/j.jviromet.2014.04.001 |pmid=24747590 |pmc=7113654 |issn=0166-0934}}</ref><ref>{{cite web | work = Public Health Agency of Canada | url = http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/coronavirus-eng.php | title = Human Coronavirus | access-date = July 22, 2015 | date = 2011-08-19 }}</ref> 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 climate]]s.  In more extreme and [[tropical climate]]s 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).<ref>{{Cite journal |last1=Golda |first1=Anna |last2=Malek |first2=Natalia |last3=Dudek |first3=Bartosz |last4=Zeglen |first4=Slawomir |last5=Wojarski |first5=Jacek |last6=Ochman |first6=Marek |last7=Kucewicz |first7=Ewa |last8=Zembala |first8=Marian |last9=Potempa |first9=Jan |last10=Pyrc |first10=Krzysztof |date=2011 |title=Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells |journal=Journal of General Virology |volume=92 |issue=6 |pages=1358–1368 |doi=10.1099/vir.0.028381-0 |issn=1465-2099 |pmc=3168281 |pmid=21325482}}</ref><ref name="Abdul-Rasool_2010" />

==Transmission==
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 [[coronavirus spike protein|spike protein]]s. HCoV-NL63, like [[SARS-CoV-1]] and [[SARS-CoV-2]], uses [[Angiotensin-converting enzyme 2]] (ACE2) as an entry receptor to bind to and enter target cells.<ref name="Hofmann_2005">{{cite journal | vauthors = Hofmann H, Pyrc K, van der Hoek L, Geier M, Berkhout B, Pöhlmann S | title = Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 22 | pages = 7988–93 | date = May 2005 | pmid = 15897467 | pmc = 1142358 | doi = 10.1073/pnas.0409465102 | bibcode = 2005PNAS..102.7988H | doi-access = free }}</ref>  And also like [[SARS-CoV-2]], HCoV-NL63 spike has a furin cleavage site, at S2′.<ref>{{cite journal |author1=Yiran Wu |author2=Suwen Zhao |title=Furin cleavage sites naturally occur in coronaviruses |journal=Stem Cell Research |date=2021 |volume=50 |issue=102115 |page=1–8 |doi=10.1016/j.scr.2020.102115 |url=https://www.sciencedirect.com/science/article/pii/S1873506120304165 |access-date=10 September 2024 |publisher=Elsevier|pmc=7836551 }}</ref>

==Diagnosis==
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.<ref name="Abdul-Rasool_2010" /> [[Viral culture]] or [[blood serum]] testing for [[antibodies]] may also be used for the confirmation of infection.

==Prevention==
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.<ref>{{cite web | work = Center for Disease Control | url = https://www.cdc.gov/coronavirus/about/ | title = About Coronavirus | access-date = July 22, 2015 }}</ref>

==Treatment and prognosis==
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]], [[Human respiratory syncytial virus|RSV]], and [[Kawasaki disease]], although it is not approved for the treatment of HCoV-NL63.<ref name="van_der_Hoek_2006" />

==Virology==
HCoV-NL63 is one of seven known coronaviruses to infect humans. The other six are:<ref name="Other Coronaviruses">{{cite web |last1=Leung |first1=Daniel |title=Coronaviruses (including SARS) |url=https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/coronaviruses-including-sars/ |website=Infectious Disease Advisor |date=20 January 2019 |publisher=Decision Support in Medicine, LLC |access-date=1 August 2020 |archive-date=16 April 2021 |archive-url=https://web.archive.org/web/20210416193956/https://www.infectiousdiseaseadvisor.com/home/decision-support-in-medicine/infectious-diseases/coronaviruses-including-sars/ |url-status=dead }}</ref>
*[[Human coronavirus 229E|Human coronavirus 229E (HCoV-229E)]]
*[[human coronavirus OC43|Human coronavirus OC43 (HCoV-OC43)]]
*[[Human coronavirus HKU1|Human coronavirus HKU1 (HCoV-HKU1)]]
*[[Middle East respiratory syndrome-related coronavirus|Middle East respiratory syndrome-related coronavirus (MERS-CoV)]]
*[[Severe acute respiratory syndrome coronavirus|Severe acute respiratory syndrome coronavirus (SARS-CoV-1)]]
*[[Severe acute respiratory syndrome coronavirus 2|Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]]

==Recent research==
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 [[aneurysm]]s of the [[coronary arteries]].<ref>{{cite journal |vauthors=Esper F, Shapiro ED, Weibel C, Ferguson D, Landry ML, Kahn JS |title=Association between a novel human coronavirus and Kawasaki disease |journal=J Infect Dis |volume=191 |issue=4 |pages=499–502 |date=February 2005 |pmid=15655771 |pmc=7199489 |doi=10.1086/428291 |url=}}</ref> In the developed world, Kawasaki disease is the most common cause of acquired [[heart disease]] in children.<ref>{{cite web | work = Mayo Clinic | url = http://www.mayoclinic.org/diseases-conditions/kawasaki-disease/basics/definition/con-20024663 | title = Kawasaki Disease | access-date = July 22, 2015 }}</ref> 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 [[Severe acute respiratory syndrome coronavirus|SARS-CoV]] (the causal agent of [[Severe acute respiratory syndrome|SARS]]) and [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]] (the causal agent of [[Coronavirus disease 2019|COVID-19]]),<ref name="Hofmann_2005" /> the latter of which can provoke [[Multisystem inflammatory syndrome in children|a similar immune response]]. HCoV-NL63 has also been found in the [[intestinal tract]] of infected individuals and linked to [[gastroenteritis]].<ref name="Fielding_2011">{{cite journal | vauthors = Fielding BC | title = Human coronavirus NL63: a clinically important virus? | journal = Future Microbiology | volume = 6 | issue = 2 | pages = 153–9 | date = February 2011 | pmid = 21366416 | doi = 10.2217/fmb.10.166 | pmc = 7079714 | doi-access = free }}</ref> 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.

==References==
{{Reflist|2}}

==External links==
* {{Wikispecies-inline|Human coronavirus NL63|''Human coronavirus NL63''}}

{{Human coronaviruses}}
{{Taxonbar|from=Q8351095}}

[[Category:Alphacoronaviruses]]
[[Category:Viral respiratory tract infections]]