Characterization of the spike protein of human coronavirus NL63 in receptor binding and pseudotype virus entry

Lin, Han Xin; Yan, Feng; Tu, Xin; Zhao, Xiongyan; Hsieh, Chih Heng; Griffin, Lauren; Junop, M.S.; Zhang, Chengsheng

doi:10.1016/j.virusres.2011.06.029

Cited by 26 publications

(27 citation statements)

References 70 publications

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“…Global and Kilifi spike sequences were aligned and compared to the HCoV-NL63 reference strain (NC_005831) to reveal the spike amino acid differences ( Figure 4A). These patterns further supported the conclusion that 2 major genotypes of HCoV-NL63 (A and B) circulated in Kilifi over the observation period ( The binding domain for the cellular receptor for HCoV-NL63 (ACE2) resides in the central portion of the spike protein, residues 476-616 [42,43], identified by the orange horizontal band marked RBD in Figure 4A top panel. Differences in this region were marked in Figure 4A with several amino acid polymorphisms persisting in multiple samples (eg, I507L, E471D, E572A), suggesting genetic drift or possible positive advantage for these residues.…”

Section: Resultssupporting

confidence: 74%

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

Kiyuka

Agoti

Munywoki

et al. 2018

The Journal of Infectious Diseases

126

112

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BackgroundHuman coronavirus NL63 (HCoV-NL63) is a globally endemic pathogen causing mild and severe respiratory tract infections with reinfections occurring repeatedly throughout a lifetime.MethodsNasal samples were collected in coastal Kenya through community-based and hospital-based surveillance. HCoV-NL63 was detected with multiplex real-time reverse transcription PCR, and positive samples were targeted for nucleotide sequencing of the spike (S) protein. Additionally, paired samples from 25 individuals with evidence of repeat HCoV-NL63 infection were selected for whole-genome virus sequencing.ResultsHCoV-NL63 was detected in 1.3% (75/5573) of child pneumonia admissions. Two HCoV-NL63 genotypes circulated in Kilifi between 2008 and 2014. Full genome sequences formed a monophyletic clade closely related to contemporary HCoV-NL63 from other global locations. An unexpected pattern of repeat infections was observed with some individuals showing higher viral titers during their second infection. Similar patterns for 2 other endemic coronaviruses, HCoV-229E and HCoV-OC43, were observed. Repeat infections by HCoV-NL63 were not accompanied by detectable genotype switching.ConclusionsIn this coastal Kenya setting, HCoV-NL63 exhibited low prevalence in hospital pediatric pneumonia admissions. Clade persistence with low genetic diversity suggest limited immune selection, and absence of detectable clade switching in reinfections indicates initial exposure was insufficient to elicit a protective immune response.

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Section: Resultssupporting

confidence: 74%

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

Kiyuka

Agoti

Munywoki

et al. 2018

The Journal of Infectious Diseases

126

112

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“…N-terminally FLAG-tagged human IFITM1, IFITM2, and IFITM3 and their mutants were also cloned into the pQCXIP vector (Clontech) between the NotI and BamHI sites (29). Plasmids expressing HCoV-OC43 S and HE proteins, VSV G protein, H1N1 IAV (A/WSN/33) HA and neuraminidase (NA), Ebola virus (EBOV) GP protein, LASV GP protein, murine leukemia virus (MLV) envelope protein, and HCoV-NL63 and SARS-CoV spike proteins were described previously (62,63). The MERS-CoV spike gene (GenBank accession number AFS88936) was synthesized by GeneScript, cloned into the pCAGGS vector, and confirmed by DNA sequence analyses.…”

Section: Methodsmentioning

confidence: 99%

Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses

Zhao

Sehgal

Hou

et al. 2018

J Virol

Self Cite

106

123

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Interferon-induced transmembrane proteins (IFITMs) are restriction factors that inhibit the infectious entry of many enveloped RNA viruses. However, we demonstrated previously that human IFITM2 and IFITM3 are essential host factors facilitating the entry of human coronavirus (HCoV) OC43. In a continuing effort to decipher the molecular mechanism underlying IFITM differential modulation of HCoV entry, we investigated the roles of structural motifs important for IFITM protein posttranslational modifications, intracellular trafficking, and oligomerization in modulating the entry of five HCoVs. We found that three distinct mutations in IFITM1 or IFITM3 converted the host restriction factors to enhance entry driven by the spike proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) and/or Middle East respiratory syndrome coronavirus (MERS-CoV). First, replacement of IFITM3 tyrosine 20 with either alanine or aspartic acid to mimic unphosphorylated or phosphorylated IFITM3 reduced its activity to inhibit the entry of HCoV-NL63 and -229E but enhanced the entry of SARS-CoV and MERS-CoV. Second, replacement of IFITM3 tyrosine 99 with either alanine or aspartic acid reduced its activity to inhibit the entry of HCoV-NL63 and SARS-CoV but promoted the entry of MERS-CoV. Third, deletion of the carboxyl-terminal 12 amino acid residues from IFITM1 enhanced the entry of MERS-CoV and HCoV-OC43. These findings suggest that these residues and structural motifs of IFITM proteins are key determinants for modulating the entry of HCoVs, most likely through interaction with viral and/or host cellular components at the site of viral entry to modulate the fusion of viral envelope and cellular membranes. The differential effects of IFITM proteins on the entry of HCoVs that utilize divergent entry pathways and membrane fusion mechanisms even when using the same receptor make the HCoVs a valuable system for comparative investigation of the molecular mechanisms underlying IFITM restriction or promotion of virus entry into host cells. Identification of three distinct mutations that converted IFITM1 or IFITM3 from inhibitors to enhancers of MERS-CoV or SARS-CoV spike protein-mediated entry revealed key structural motifs or residues determining the biological activities of IFITM proteins. These findings have thus paved the way for further identification of viral and host factors that interact with those structural motifs of IFITM proteins to differentially modulate the infectious entry of HCoVs.

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“…Studies have shown that, at least in SARS-CoV, a receptor-binding domain on the S protein mediates the attachment of said virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2) [33,34]. Lin et al found that HCoV-NL63 also makes use of the S protein-ACE2 mechanism for cell entry [35].…”

Section: Coronavirusesmentioning

confidence: 99%

Human coronaviruses: Clinical features and phylogenetic analysis

Lin

2013

BioMedicine

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Keywords: human betacoronavirus 2c EMC2012 human coronavirus phylogenetic tree severe acute respiratory syndrome coronavirus (SARS-CoV) a b s t r a c t Strains of human coronavirus (HCoV), namely HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, primarily infect the upper respiratory and gastrointestinal tracts and are the most common cause of non-rhinovirus-induced common cold in humans. Although the manifestations of coronavirus infection (i.e., rhinorrhea, sneezing, cough, nasal obstruction, and bronchitis) are generally self-limiting in healthy adults, certain strains such as HCoV-NL63 and HCoV-HKU1 can cause severe lower respiratory tract infection and febrile seizure, especially in infants, people of advanced age, and immunocompromised hosts. In 2003, a novel HCoV strain was identified as the causative agent of the severe acute respiratory syndrome (SARS) epidemic that began in Asia in 2002. The strain has hence been referred to as SARS-CoV. In addition, as recently as September 2012, another novel HCoV, human betacoronavirus 2c EMC2012, was identified as being the cause of fever, renal failure, pneumonia, and severe respiratory distress in two patients in the Middle East.Phylogenetic analysis has revealed highly conserved sequences of ORF1ab, spike, nucleocapsid, and envelope protein genes, but not membrane protein genes, between human betacoronavirus 2c EMC2012 and SARS-CoV. This review focuses on the differences in the genomes of certain HCoV strains, the pathogenesis of said strains, and recent developments in the establishment of therapeutic agents that might aid in the treatment of patients with such infections.

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Characterization of the spike protein of human coronavirus NL63 in receptor binding and pseudotype virus entry

Cited by 26 publications

References 70 publications

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya

Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses

Human coronaviruses: Clinical features and phylogenetic analysis

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