More and More Coronaviruses: Human Coronavirus HKU1

Abstract

After human coronaviruses OC43, 229E and NL63, human coronavirus HKU1 (HCoV-HKU1) is the fourth human coronavirus discovered. HCoV-HKU1 is a group 2a coronavirus that is still not cultivable. The G + C contents of HCoV-HKU1 genomes are 32%, the lowest among all known coronaviruses with complete genome sequences available. Among all coronaviruses, HCoV-HKU1 shows the most extreme codon usage bias, attributed most importantly to severe cytosine deamination. All HCoV-HKU1 genomes contain unique tandem copies of a 30-base acidic tandem repeat of unknown function at the N-terminus of nsp3 inside the acidic domain upstream of papain-like protease 1. Three genotypes, A, B and C, of HCoV-HKU1 and homologous recombination among their genomes, are observed. The incidence of HCoV-HKU1 infections is the highest in winter. Similar to other human coronaviruses, HCoV-HKU1 infections have been reported globally, with a median (range) incidence of 0.9 (0 - 4.4) %. HCoV-HKU1 is associated with both upper and lower respiratory tract infections that are mostly self-limiting. The most common method for diagnosing HCoV-HKU1 infection is RT-PCR or real-time RT-PCR using RNA extracted from respiratory tract samples such as nasopharyngeal aspirates (NPA). Both the pol and nucleocapsid genes have been used as the targets for amplification. Monoclonal antibodies have been generated for direct antigen detection in NPA. For antibody detection, Escherichia coli BL21 and baculovirus-expressed recombinant nucleocapsid of HCoV-HKU1 have been used for IgG and IgM detection in sera of patients and normal individuals, using Western blot and enzyme-linked immunoassay.

Keywords: HKU1; coronavirus; human; novel.

Figure 1.

Phylogenetic analysis of RNA-dependent RNA polymerases of coronaviruses with complete genome sequences available by the end of 2008. The tree was constructed by neighbor joining method using Kimura's two-parameter correction and bootstrap values calculated from 1000 trees. Nine hundred and fifty eight amino acid positions were included in the analysis. The scale bar indicates the estimated number of substitutions per 50 amino acids. HCoV-229E, human coronavirus 229E (NC_002645); PEDV, porcine epidemic diarrhea virus (NC_003436); TGEV, porcine transmissible gastroenteritis virus (NC_002306); FCoV, feline coronavirus (AY994055); PRCV, porcine respiratory coronavirus (DQ811787); HCoV-NL63, human coronavirus NL63 (NC_005831); bat-CoV-HKU2 (EF203064), HKU4 (NC_009019), HKU5 (NC_009020), HKU8 (NC_010438), HKU9 (NC_009021), 1A (NC_010437), 1B (NC_010436), 512/2005 (NC_009657); HCoV-HKU1, human coronavirus HKU1 (NC_006577), HCoV-OC43, human coronavirus OC43 (NC_005147); MHV, mouse hepatitis virus (NC_006852); BCoV, bovine coronavirus (NC_003045); PHEV, porcine hemagglutinating encephalomyelitis virus (NC_007732); ECoV, equine coronavirus (NC_010327); SARS-CoV, SARS coronavirus (NC_004718); bat-SARS-CoV-HKU3, bat-SARS coronavirus HKU3 (NC_009694); IBV, infectious bronchitis virus (NC_001451); TCoV, turkey coronavirus (NC_010800); SW1, beluga whale coronavirus (NC_010646); BuCoV-HKU11, Bulbul coronavirus HKU11 (NC_011548); ThCoV-HKU12, Thrush coronavirus HKU12 (NC_011549); MuCoV-HKU13, Munia coronavirus HKU13 (NC_011550).

Figure 2.

Genome organization of HCoV-HKU1. Predicted ORF 1ab, encoding the nonstructural polyproteins (nsp1 to nsp16) and ORFs encoding the HE, S, E, M and N structural proteins are indicated. Arrows indicate putative cleavage sites (with the corresponding nucleotide positions) of the replicase polyprotein encoded by ORF 1ab (amino acids at boundaries also shown) and S protein. Putative positions of TRS are marked by▪. Major parts of ORF 1ab (PL1^pro, PL2^pro, 3CL^pro, pol and helicase) encoding key enzymatic activities are colored in yellow. ATR represents the acidic tandem repeat in nsp3.