Human Coronavirus NL63 Infection in Canada

Bastien, Nathalie; Anderson, Kelly K.; Hart, Laura; Caeseele, Paul Van; Brandt, Ken; Milley, Doug; Hatchette, Todd F.; Weiss, Elise; Li, Yan

doi:10.1086/426869

Cited by 161 publications

(189 citation statements)

References 11 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…HCoV-NL63 engages the same receptor and, consequently, infects the same target cells as SARS-CoV, but, in contrast to SARS-CoV, the virus usually induces only mild or moderate respiratory disease (31)(32)(33)(34). However, HCoV-NL63 was also detected in infants and immunocompromised adults with relatively severe RTI (7,8,35), suggesting that infection might have more profound pathogenic effects in individuals with reduced immune defenses.…”

Section: Discussionmentioning

confidence: 99%

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Hofmann

Pyrć

Hoek

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

728

699

View full text Add to dashboard Cite

Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63-but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.C oronaviruses (CoVs) are enveloped RNA viruses that are grouped according to genome sequence and serology (1). Human CoVs (HCoVs) 229E and OC43 are members of groups I and II, respectively, and infection with these viruses is thought to be responsible for Ϸ30% of common-cold cases (1). In contrast, infection with severe acute respiratory syndrome (SARS)-CoV causes a severe respiratory tract illness (RTI) that is fatal in Ϸ10% of infected individuals (2, 3). The factors that determine the pathogenicity of CoVs are incompletely understood; however, a role for the spike (S) protein has been suggested (4). The S proteins of CoVs, which provide virions with a corona-like appearance, mediate infection of target cells and play a central role in viral replication (4). The interaction of CoV S proteins with specific cellular receptors determines, to a large extent, which cells can be infected (5), and the entry process is an attractive target for antiviral therapy (6).Recently, a HCoV termed NL63 was discovered in infants and immunocompromised adults with RTI (7, 8). HCoV-NL63 is a group I CoV and is most closely related to HCoV-229E (7-9). HCoV-229E employs CD13 (aminopeptidase N) as a receptor for infection of target cells (10,11). Because the NL63-and 229E-S proteins share 56% amino acid identity (7), it is conceivable that HCoV-NL63 also engages CD13 for infectious cellular entry. However, the HCoV-NL63-S protein contains a unique, 179-aa sequence at its N terminus that does not share homology with other known CoV proteins and that might alter the re...

show abstract

Section: Discussionmentioning

confidence: 99%

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Hofmann

Pyrć

Hoek

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

728

699

View full text Add to dashboard Cite

show abstract

“…NL63 has been found to be associated with diseases in the upper and lower respiratory tracts, such as bronchiolitis, conjunctivitis, croup and pneumonia in young children and immunocompromised adults (Arden et al, 2005;Bastien et al, 2005;Ebihara et al, 2005;Gerna et al, 2006;Kaiser et al, 2005;van der Hoek et al, 2005. So far, NL63 infections have been reported in 12 countries across Europe, Asia and North America, indicating that it is circulating among the human population worldwide (Arden et al, 2005;Bastien et al, 2005;Han et al, 2007;Koetz et al, 2006;Lau et al, 2006;Suzuki et al, 2005;Vabret et al, 2005).NL63 is a member of the group I coronaviruses, which also includes HCoV-229E (229E), feline infectious peritonitis virus 79-1146, feline enteric coronavirus 79-1683, canine coronavirus and porcine transmissible gastroenteritis virus (TGEV) (van der Hoek et al, 2004. The genome of NL63 contains 27553 nt and encodes the polyproteins 1a Sturman & Holmes, 1984).…”

mentioning

confidence: 99%

Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction

Lin

Yan

Wong

et al. 2008

Journal of General Virology

Self Cite

View full text Add to dashboard Cite

Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause acute respiratory diseases in young children and immunocompromised adults. Like severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the human angiotensinconverting enzyme 2 (hACE2) receptor for cellular entry. To identify residues in the spike protein of NL63 that are important for hACE2 binding, this study first generated a series of S1-truncated variants, examined their associations with the hACE2 receptor and subsequently mapped a minimal receptor-binding domain (RBD) that consisted of 141 residues (aa 476-616) towards the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD bound to hACE2 more efficiently than its full-length counterpart and had a binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of RBD variants was generated using site-directed mutagenesis and random mutant library screening assays, and identified 15 residues (C497, Y498, V499, C500, K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that appeared to be critical for the RBD-hACE2 association. These critical residues clustered in three separate regions (designated RI, RII and RIII) inside the RBD, which may represent three receptor-binding sites. These results may help to delineate the molecular interactions between the S protein of NL63 and the hACE2 receptor, and may also enhance our understanding of the pathogenesis of NL63 and SARS-CoV. INTRODUCTIONCoronaviruses consist of a large and diverse family of enveloped, positive-sense, single-stranded RNA viruses. They can infect a broad range of mammalian and avian species, causing a variety of diseases in the respiratory, gastrointestinal, hepatic and central nervous systems (Holmes & Lai, 1996). The outbreak of severe acute respiratory syndrome (SARS) in [2002][2003], which was caused by a highly pathogenic virus named SARS coronavirus (SARS-CoV), posed significant challenges to medical communities worldwide (Ksiazek et al., 2003;Peiris et al., 2003). Since then, two additional human coronaviruses, HCoV-NL63 (NL63) and HCoV-HKU1, have been identified (van der Hoek et al., 2004;Woo et al., 2005). NL63 has been found to be associated with diseases in the upper and lower respiratory tracts, such as bronchiolitis, conjunctivitis, croup and pneumonia in young children and immunocompromised adults (Arden et al., 2005;Bastien et al., 2005;Ebihara et al., 2005;Gerna et al., 2006;Kaiser et al., 2005;van der Hoek et al., 2005. So far, NL63 infections have been reported in 12 countries across Europe, Asia and North America, indicating that it is circulating among the human population worldwide (Arden et al., 2005;Bastien et al., 2005;Han et al., 2007;Koetz et al., 2006;Lau et al., 2006;Suzuki et al., 2005;Vabret et al., 2005).NL63 is a member of the group I coronaviruses, which also includes HCoV-229E (229E), feline infectious peritonitis virus 79-1146, feline enteric coronavirus 79-1683, canine coronavirus and porcine transmissible ga...

show abstract

“…Nested PCR assays were used to detect KIPyV and WUPyV using the primers originally described by Allander et al (2) and Gaynor et al (8). In addition, we screened KIPyV-and WUPyV-positive specimens for human metapneumovirus, respiratory syncytial virus (RSV), influenza virus A and B, parainfluenza virus types 1 to 3 (PIV1 to -3), human rhinoviruses, and human coronaviruses (229E, OC43, NL63, and HKU1) using a standard reverse transcription-PCR technique (4,5,13,14) and for adenovirus and human bocavirus (HBoV) using traditional PCR methods (3,10). All of the PCR products were sequenced to confirm the specificity of each virus.…”

mentioning

confidence: 99%

Prevalence of Human KI and WU Polyomaviruses in Children with Acute Respiratory Tract Infection in China

Yuan

Xie

et al. 2008

J Clin Microbiol

View full text Add to dashboard Cite

The KI and WU polyomaviruses were found in 11 (2.7%) and 17 (4.2%) of 406 nasopharyngeal aspirates, respectively, from children with acute respiratory tract infection (ARTI). The phylogenetic analysis indicates that they are all in the same cluster as the prototype strains. Our findings suggest that they are common in children with ARTI in China.In 1971, two human polyomavirus species named BK and JC were first isolated (7, 12). These two viruses are ubiquitous in most human populations and can cause persistent subclinical infections in healthy individuals and then reactivate under immunocompromised conditions. Recently, two novel human polyomaviruses were found, KI polyomavirus (KIPyV) in 6 (1%) of 637 nasopharyngeal aspirates (NPA) and 1 (0.5%) of 192 fecal samples in Sweden (2) and WU polyomavirus (WUPyV) in 43 (2%) of 2,135 patients with acute respiratory tract infection (ARTI) in Australia and the United States (8).

show abstract

Human Coronavirus NL63 Infection in Canada

Cited by 161 publications

References 11 publications

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD–ACE2 receptor interaction

Prevalence of Human KI and WU Polyomaviruses in Children with Acute Respiratory Tract Infection in China

Contact Info

Product

Resources

About