Human coronavirus NL63

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 a seven-month-old child with bronchiolitis in the Netherlands.[1] The virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to ACE2.[2][3] 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.[1]

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

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.[4] The virus originated from infected palm civets and bats.[5] Estimates of its divergence from another coronavirus (HCoV-229E) are around 1000 years ago: it has likely circulated in humans for centuries.[6]

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.[7] Recombinant viruses can arise when two viral genomes 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. 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.[8] However, the high frequency of croup is specific to HCoV-NL63 infection.

Cause
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 solutions at room temperature and three hours on dry surfaces.[9] Most people will be infected with a coronavirus in their lifetime, but some populations are more susceptible to HCoV-NL63. These population 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).[1]

Mechanism

Transmission of HCoV-NL63 is likely through droplet expulsion from the respiratory tract, which may be airborne or spread through close personal contact. The virus is able to survive for up to seven days in respiratory secretions and remains infective at room temperature.[10] Once the virus has entered the host it binds to cellular receptors using spike proteins, similar to those found in HIV-1. The virus is able to use Angiotensin-converting enzyme 2 (ACE2) as an entry receptor to bind to and enter target cells.[10] No determination of the specific entry of the virus into the host cell has been completed. Therefore, entrance into the cell is either through direct cell fusion with the plasma membrane or endocytosis followed by fusion with the membrane. Due to the lack of a cDNA clone of HCoV-NL63, research on the replication cycle is limited. Because it is a positive single-stranded RNA virus, the processes of replication via transcription and translation can be carried out in the cytoplasm of the infected cell.

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.[1] 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.[11]

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, RSV, and Kawasaki disease.[4]

Virology

HCoV-NL63 is one of seven known coronaviruses to infect humans. The other six are[12]:

Recent research

Recent data suggest an association of HCoV-NL63 infection with Kawasaki disease, a systemic vasculitis in childhood that may result in aneurysms of the coronary arteries. In the developed world, Kawasaki disease is the most common cause of acquired heart disease in children.[13] Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because of recent evidence that this virus uses the same cellular receptor as SARS-CoV (ACE2).[10] HCoV-NL63 has also been found in the intestinal tract of infected individuals and linked to gastroenteritis.[14] 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.

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References
  1. 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. "ACE2 angiotensin I converting enzyme 2 - Gene". NCBI. 2020-02-28. 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).
  3. Fehr AR, Perlman S (2015). Maier HJ, Bickerton E, Britton P (eds.). "Coronaviruses: an overview of their replication and pathogenesis". Methods in Molecular Biology. Springer. 1282: 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC 4369385. PMID 25720466.
  4. 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. PMID 16911043.
  5. 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.
  6. Pyrc, K (2006). "Mosaic structure of human coronavirus NL63, one thousand years of evolution". J. Mol. Biol. 364: 964–973. ISSN 0022-2836.
  7. Tao Y, Shi M, Chommanard C, Queen K, Zhang J, Markotter W, Kuzmin IV, Holmes EC, Tong S. Surveillance of Bat Coronaviruses in Kenya Identifies Relatives of Human Coronaviruses NL63 and 229E and Their Recombination History. J Virol. 2017 Feb 14;91(5):e01953-16. doi: 10.1128/JVI.01953-16. Print 2017 Mar 1. PMID: 28077633
  8. 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. PMID 15962232.
  9. "Human Coronavirus". Public Health Agency of Canada. 2011-08-19. Retrieved July 22, 2015.
  10. 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.
  11. "About Coronavirus". Center for Disease Control. Retrieved July 22, 2015.
  12. Leung, Daniel. "Coronaviruses (including SARS)". Infectious Disease Advisor. Decision Support in Medicine, LLC. Retrieved 1 August 2020.
  13. "Kawasaki Disease". Mayo Clinic. Retrieved July 22, 2015.
  14. Fielding BC (February 2011). "Human coronavirus NL63: a clinically important virus?". Future Microbiology. 6 (2): 153–9. doi:10.2217/fmb.10.166. PMID 21366416.
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