Understanding Human Coronavirus HCoV-NL63

Abdul-Rasool, Sahar; Fielding, Burtram C

Unlike the SARS-CoV genome, the HCoV-NL63 genome encodes for only one accessory protein, ORF3 ( Fig. 1) . ORF3 is expressed from distinct subgenomic (sg) mRNA 3, which is one of at least six distinct mRNAs [4] . The ORF3 gene encodes for a putative 225 amino acid protein, about 25.6 kDa in size. Pyrc et al. (2004) reports that the HCoV-NL63 ORF3 gene has a unique nucleotide composition and appears as a U-rich and A-poor region within the genome, indicating a recent gene transfer event from another viral or cellular origin [4] . The ORF3 protein of HCoV-NL63 is homologous to proteins of the other Group 1 coronaviruses, with an amino acid sequence most similar (43% identity and 62% similarity) to HCoV-229E ORF4. Based on comparative in silico analysis of HCoV-NL63 ORF3 and other human coronavirus ORF3-like homologues, Fielding and Suliman speculate that the protein could contribute to pathogenesis in the natural host [39] . More recently, studies have shown that HCoV-NL63 localizes along the secretory pathway (ERGIC, Golgi, plasma membrane) and colocalizes with the structural proteins M and E in the ERGIC. Also, studies have shown that this N-glycosylated protein is incorporated into virions during assembly. This further suggests an important function for HCoV-NL63 ORF3, particularly in virus assembly and/or budding from the infected cell [40] .