Human coronavirus HKU1 (HCoV-HKU1,Betacoronavirus hongkongense)[1] is a species ofcoronavirus in humans and animals. It causes an upper respiratory disease with symptoms of thecommon cold, but can advance topneumonia andbronchiolitis.[2] It was first discovered in January 2004 from one man inHong Kong.[3] Subsequent research revealed it has global distribution and earlier genesis.
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 themouse hepatitis virus (MHV), and is distinct in that regard from other known humanbetacoronaviruses, such asHCoV-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 theRNA-dependent RNA polymerase (RdRp),spike (S), andnucleocapsid (N) genes were analyzed, incompatible phylogenetic relationships were discovered. Complete genome sequencing of 22 strains of HCoV-HKU1 confirmed this was due to naturalrecombination.[3] HCoV-HKU1 likely originated fromrodents.[12]
HCoV-HKU1 is one of seven known coronaviruses to infect humans. The other six are:[13]
The structures of HCoV-HKU1 spike (S) andhemagglutinin esterase (HE) proteins have been resolved byCryo-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 vestigiallectin domain. This domain is shielded from recognition by the immune system via size changes and glycosylation.[15]
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 inNorthern 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 atYale-New Haven Hospital inNew 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 likehuman respiratory syncytial virus (RSV),parainfluenza viruses (types 1–3),influenza A and B viruses, andadenovirus bydirect immunofluorescence assay as well ashuman metapneumovirus andHCoV-NH byreverse 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 withHCoV-NH (New Haven coronavirus), which is a strain ofHuman 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]
^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".bioRxiv10.1101/2023.04.20.536837.
^Leung, Daniel (20 January 2019)."Coronaviruses (including SARS)".Infectious Disease Advisor. Decision Support in Medicine, LLC. Archived fromthe original on 16 April 2021. Retrieved1 August 2020.