Background
Human coronavirus HKU1 (HCoV-HKU1) was first isolated in 2005 from a sample of a pneumonia patient in Hong Kong. This strain was named after the University of Hong Kong (HKU), reflecting the location and institution where it was first isolated. The discovery of HCoV-HKU1 is significant in human coronavirus (HCoV) research as it added to the known types of coronaviruses and further enriched the classification of the coronavirus family. HKU1 is a spherical coronavirus with virion particles approximately 80-120 nm in diameter. Like other coronaviruses, HKU1 is decorated with spike (S) proteins on its surface, which allow the virus to bind to receptors on host cells. Inside the viral envelope, the genomic RNA is associated with the nucleocapsid (N) protein, forming a helical symmetrical nucleocapsid. The N protein plays a crucial role in the virus's replication process, binding to genomic RNA as a dimer to form the helical nucleocapsid. Modifications such as phosphorylation, SUMOylation, and ADP-ribosylation of the N protein have been observed in HKU1, affecting viral replication and evasion of host immune responses. The genome of HKU1 is a single-stranded positive-sense RNA, over 30 kb in length, making it one of the largest viral RNA genomes known. It includes a 5'-cap structure and a 3'-polyadenylated tail, with the capacity to encode viral replicase. The HKU1 genome comprises two untranslated regions (UTRs), with the 5'-UTR being 205 nucleotides long and the 3'-UTR being 281 nucleotides long.
Figure 1. Genomic Structure of Human Coronaviruses (HCoV) (Source: Liu DX, et al., 2021)
The replication cycle of HKU1 can be divided into five main steps: attachment, entry and uncoating, expression of viral replicase and formation of the transcription complex, viral RNA synthesis, and viral assembly and release. HKU1 attaches to host cell receptors via its S protein, promoting fusion of the virus with the cell membrane. Viral RNA serves as a template for the translation of polyproteins pp1a and pp1ab, which are then cleaved into non-structural proteins (nsps) and form the viral replication and transcription complex (RTC) in the cell membrane. Viral RNA is replicated through a negative-sense intermediate and produces nested subgenomic RNAs (sgRNAs) via discontinuous transcription. Viral particles assemble in the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) and are ultimately released into the extracellular space through exocytosis. The receptor binding of HKU1 is critical for viral infection. Like other coronaviruses, HKU1 uses carbohydrates or proteins on the cell membrane as receptors. HKU1 primarily initiates infection by binding to glycoconjugate receptors carrying 9-O-acetylated sialic acid. Proteolysis of the S protein also plays an important role in viral entry, facilitated by protease-like serine proteases, which enhances the virus's fusion ability.
HKU1 infections are widespread globally. The primary mode of transmission is through airborne droplets, particularly more active during the winter flu season. Clinical symptoms of HKU1 infection include nasal discharge, cough, sore throat, and fever, generally similar to those caused by other respiratory viruses. Approximately 50% of HKU1-infected patients may experience febrile seizures. HKU1 infections are also associated with co-circulation with respiratory syncytial virus, often peaking before influenza seasons, and may be linked to exacerbations of wheezing and asthma. Diagnosing HKU1 infections is challenging because its symptoms are difficult to distinguish from those caused by other respiratory viruses. Confirmation typically requires specific virological tests, such as PCR or viral isolation experiments. The potential for reinfection with HKU1 indicates that the virus does not induce long-lasting protective immunity, making research into its epidemiology and clinical manifestations particularly important. Detailed study of HKU1 will help us better understand coronavirus variability, transmission, and public health impact, and aid in the development of effective vaccines and treatments to address potential future outbreaks.
Alternative Names
Human Coronavirus HKU1 N Protein His Tag
HKU1 N Protein Recombinant
Human Coronavirus HKU1 N Protein Antigen
Coronavirus HKU1 N Protein
HCoV-HKU1 N Protein
References
- 1. Liu DX, et al. Human coronavirus-229E, -OC43, -NL63, and -HKU1 (Coronaviridae). Encyclopedia of Virology. 2021;428-440.