Human coronavirus HKU1

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Human coronavirus HKU1
Coronavirus-HKU1.png
Formation of HcoV-HKU1
Virus classification OOjs UI icon edit-ltr.svg
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Embecovirus
Species:
Betacoronavirus hongkonense
Synonyms
  • Human coronavirus HKU1
  • HCoV-HKU1

Human coronavirus HKU1 (HCoV-HKU1, Betacoronavirus hongkonense) [1] is a species of coronavirus in humans and animals. It causes an upper respiratory disease with symptoms of the common cold, but can advance to pneumonia and bronchiolitis. [2] It was first discovered in January 2004 from one man in Hong Kong. [3] Subsequent research revealed it has global distribution and earlier genesis.

Contents

The virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to the N-acetyl-9-O-acetylneuraminic acid receptor. [4] It has the Hemagglutinin esterase (HE) gene, which distinguishes it as a member of the genus Betacoronavirus and subgenus Embecovirus . [5]

History

HCoV-HKU1 was first detected in January 2004, in a 71-year-old man who was hospitalized due to acute respiratory distress syndrome and radiographically confirmed bilateral pneumonia. The man had recently returned to Hong Kong from Shenzhen, China. [3] [6]

In 2024, the species that HCoV-HKU1 belongs to was renamed Betacoronavirus hongkonense. [7]

Virology

Woo and coworkers were unsuccessful in their attempts to grow a HCoV-HKU1 isolate but were able to obtain the complete genomic sequence. Phylogenetic analysis showed that HKU1 is most closely related to the mouse hepatitis virus (MHV), and is distinct in that regard from other known human betacoronaviruses, such as HCoV-OC43. [3] The virus has been successfully cultured by Pyrc and coworkers in the ex vivo model of human respiratory epithelium. [8] Additional research has revealed that the virus attaches itself to O-acetylated sialic acids on the cell surface, [9] which instigates a conformational shift in the S protein, facilitating interaction with the entry receptor. [10] Intriguingly, the enzyme kallikrein 13 has been identified as an activating factor responsible for the spike protein processing by the Pyrc's team. This could potentially specify the virus's tissue and cellular preference, and might also govern the regulation of interspecies transmission. [11]

When the RNA-dependent RNA polymerase (RdRp), spike (S), and nucleocapsid (N) genes were analyzed, incompatible phylogenetic relationships were discovered. Complete genome sequencing of 22 strains of HCoV-HKU1 confirmed this was due to natural recombination. [3] HCoV-HKU1 likely originated from rodents. [12]

HCoV-HKU1 is one of seven known coronaviruses to infect humans. The other six are: [13]

The structures of HCoV-HKU1 spike (S) and hemagglutinin esterase (HE) proteins have been resolved by Cryo-EM in 2016 and 2020, respectively. The S protein ( PDB: 5I08 ​) has been noted for its large size. [14] The HE protein ( PDB: 6Y3Y ​) differs from conventional ones (such as the one in OC43) by having a much smaller vestigial lectin domain. This domain is shielded from recognition by the immune system via size changes and glycosylation. [15]

Epidemiology

A trace-back analysis of SARS negative nasopharyngeal aspirates from patients with respiratory illness during the SARS period in 2003, identified the presence of CoV-HKU1 RNA in the sample from a 35-year-old woman with pneumonia. [16]

Following the initial reports of the discovery of HCoV-HKU1, the virus was identified that same year in 10 patients in northern Australia. Respiratory samples were collected between May and August (winter in Australia). Investigators found that most of the HCoV-HKU1–positive samples originated from children in the later winter months. [17]

The first known cases in the Western hemisphere were discovered in 2005 after analysing older specimens by clinical virologists at Yale-New Haven Hospital in New Haven, Connecticut who were curious to discover if HCoV-HKU1 was in their area. They conducted a study of specimens collected in a 7-week period (December 2001 – February 2002) in 851 infants and children. Specimens of nine children had human coronavirus HKU1. These children had respiratory tract infections at the time the specimens were collected (in one girl so severe that mechanical ventilation was needed), while testing negative for other causes like Human respiratory syncytial virus (RSV), parainfluenza viruses (types 1–3), influenza A and B viruses, and adenovirus by direct immunofluorescence assay as well as human metapneumovirus and HCoV-NH by reverse transcription polymerase chain reaction (RT-PCR). The researchers reported that the strains identified in New Haven were similar to the strain found in Hong Kong and suggested a worldwide distribution. [18] These strains found in New Haven is not to be confused with HCoV-NH (New Haven coronavirus), which is a strain of Human coronavirus NL63.

In July 2005, six cases were reported in France. In these cases, French investigators utilized improved techniques for recovering the virus from nasopharyngeal aspirates and from stool samples. [19]

See also

References

  1. ↑ "Taxon Details | ICTV". International Committee on Taxonomy of Viruses (ICTV). Retrieved 25 July 2024.
  2. ↑ 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.
  3. 1 2 3 4 Woo, P. C. Y.; Lau, S. K. P.; Chu, C.-m.; Chan, K.-h.; Tsoi, H.-w.; Huang, Y.; Wong, B. H. L.; Poon, R. W. S.; Cai, J. J.; Luk, W.-k.; Poon, L. L. M.; Wong, S. S. Y.; Guan, Y.; Peiris, J. S. M.; Yuen, K.-y. (2004). "Characterization and Complete Genome Sequence of a Novel Coronavirus, Coronavirus HKU1, from Patients with Pneumonia". Journal of Virology. 79 (2): 884–95. doi:10.1128/JVI.79.2.884-895.2005. PMC   538593 . PMID   15613317.
  4. ↑ 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.
  5. ↑ Woo, Patrick C. Y.; Huang, Yi; Lau, Susanna K. P.; Yuen, Kwok-Yung (2010-08-24). "Coronavirus Genomics and Bioinformatics Analysis". Viruses. 2 (8): 1804–1820. doi: 10.3390/v2081803 . ISSN   1999-4915. PMC   3185738 . PMID   21994708. In all members of Betacoronavirus subgroup A, a haemagglutinin esterase (HE) gene, which encodes a glycoprotein with neuraminate O-acetyl-esterase activity and the active site FGDS, is present downstream to ORF1ab and upstream to S gene (Figure 1).
  6. ↑ Lau, S. K. P.; Woo, P. C. Y.; Yip, C. C. Y.; Tse, H.; Tsoi, H.-w.; Cheng, V. C. C.; Lee, P.; Tang, B. S. F.; Cheung, C. H. Y.; Lee, R. A.; So, L.-y.; Lau, Y.-l.; Chan, K.-h.; Yuen, K.-y. (2006). "Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong". Journal of Clinical Microbiology. 44 (6): 2063–71. doi:10.1128/JCM.02614-05. PMC   1489438 . PMID   16757599.
  7. ↑ "History of the taxon: Species: Betacoronavirus hongkonense (2024 Release, MSL #40)". International Committee on Taxonomy of Viruses. Retrieved 9 April 2025.
  8. ↑ Pyrc, Krzysztof; Sims, Amy C.; Dijkman, Ronald; Jebbink, Maarten; Long, Casey; Deming, Damon; Donaldson, Eric; Vabret, Astrid; Baric, Ralph; van der Hoek, Lia; Pickles, Raymond (November 2010). "Culturing the Unculturable: Human Coronavirus HKU1 Infects, Replicates, and Produces Progeny Virions in Human Ciliated Airway Epithelial Cell Cultures". Journal of Virology. 84 (21): 11255–11263. doi:10.1128/JVI.00947-10. ISSN   0022-538X. PMC   2953148 . PMID   20719951.
  9. ↑ Huang, Xingchuan; Dong, Wenjuan; Milewska, Aleksandra; Golda, Anna; Qi, Yonghe; Zhu, Quan K.; Marasco, Wayne A.; Baric, Ralph S.; Sims, Amy C.; Pyrc, Krzysztof; Li, Wenhui; Sui, Jianhua (2015-07-15). Perlman, S. (ed.). "Human Coronavirus HKU1 Spike Protein Uses O -Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme". Journal of Virology. 89 (14): 7202–7213. doi:10.1128/JVI.00854-15. ISSN   0022-538X. PMC   4473545 . PMID   25926653.
  10. ↑ Pronker, Matti F.; Creutznacher, Robert; Drulyte, Ieva; Hulswit, Ruben J.G.; Li, Zeshi; Van Kuppeveld, Frank J.M.; Snijder, Joost; Lang, Yifei; Bosch, Berend-Jan; Boons, Geert-Jan; Frank, Martin; Groot, Raoul J. de; Hurdiss, Daniel L. (2023). "Sialoglycan binding triggers spike opening in a human coronavirus". bioRxiv   10.1101/2023.04.20.536837 .
  11. ↑ Milewska, Aleksandra; Falkowski, Katherine; Kulczycka, Magdalena; Bielecka, Ewa; Naskalska, Antonina; Mak, Pawel; Lesner, Adam; Ochman, Marek; Urlik, Maciej; Diamandis, Elftherios; Prassas, Ioannis; Potempa, Jan; Kantyka, Tomasz; Pyrc, Krzysztof (2020-11-24). "Kallikrein 13 serves as a priming protease during infection by the human coronavirus HKU1". Science Signaling. 13 (659). doi:10.1126/scisignal.aba9902. ISSN   1945-0877. PMC   7857416 . PMID   33234691.
  12. ↑ Fung, To Sing; Liu, Ding Xiang (2019). "Human Coronavirus: Host-Pathogen Interaction". Annual Review of Microbiology. 73: 529–557. doi: 10.1146/annurev-micro-020518-115759 . PMID   31226023.
  13. ↑ 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.
  14. ↑ Kirchdoerfer, Robert N.; Cottrell, Christopher A.; Wang, Nianshuang; Pallesen, Jesper; Yassine, Hadi M.; Turner, Hannah L.; Corbett, Kizzmekia S.; Graham, Barney S.; McLellan, Jason S.; Ward, Andrew B. (March 2016). "Pre-fusion structure of a human coronavirus spike protein". Nature. 531 (7592): 118–121. Bibcode:2016Natur.531..118K. doi: 10.1038/nature17200 . PMC   4860016 . PMID   26935699.
  15. ↑ Hurdiss DL, Drulyte I, Lang Y, Shamorkina TM, Pronker MF, van Kuppeveld FJ, Snijder J, de Groot RJ (16 November 2020). "Cryo-EM structure of coronavirus-HKU1 haemagglutinin esterase reveals architectural changes arising from prolonged circulation in humans". Nature Communications. 11 (1): 4646. Bibcode:2020NatCo..11.4646H. doi: 10.1038/s41467-020-18440-6 . PMC   7495468 . PMID   32938911.
  16. ↑ Woo, Patrick C. Y.; Lau, Susanna K. P.; Chu, Chung-ming; Chan, Kwok-hung; Tsoi, Hoi-wah; Huang, Yi; Wong, Beatrice H. L.; Poon, Rosana W. S.; Cai, James J.; Luk, Wei-kwang; Poon, Leo L. M.; Wong, Samson S. Y.; Guan, Yi; Peiris, J. S. Malik; Yuen, Kwok-yung (January 2005). "Characterization and complete genome sequence of a novel coronavirus, coronavirus HKU1, from patients with pneumonia". Journal of Virology. 79 (2): 884–895. doi:10.1128/JVI.79.2.884-895.2005. ISSN   0022-538X. PMC   538593 . PMID   15613317.
  17. ↑ Sloots, T; McErlean, P; Speicher, D; Arden, K; Nissen, M; MacKay, I (2006). "Evidence of human coronavirus HKU1 and human bocavirus in Australian children". Journal of Clinical Virology. 35 (1): 99–102. doi: 10.1016/j.jcv.2005.09.008 . PMC   7108338 . PMID   16257260.
  18. ↑ Esper, Frank; Weibel, Carla; Ferguson, David; Landry, Marie L.; Kahn, Jeffrey S. (2006). "Coronavirus HKU1 Infection in the United States". Emerging Infectious Diseases. 12 (5): 775–9. doi:10.3201/eid1205.051316. PMC   3374449 . PMID   16704837.
  19. ↑ Vabret, A.; Dina, J.; Gouarin, S.; Petitjean, J.; Corbet, S.; Freymuth, F. (2006). "Detection of the New Human Coronavirus HKU1: A Report of 6 Cases". Clinical Infectious Diseases. 42 (5): 634–9. doi: 10.1086/500136 . PMC   7107802 . PMID   16447108.
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