Discovery of a subgenotype of human coronavirus NL63 associated with severe lower respiratory tract infection in China, 2018

Emerg Microbes Infect. 2020 Jan 29;9(1):246-255. doi: 10.1080/22221751.2020.1717999. eCollection 2020.


Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.

Keywords: human coronavirus NL63; new subgenotype; phylogenetic analysis; pneumonia; viral entry; whole-genome sequencing.

MeSH terms

  • Child, Preschool
  • China
  • Coronavirus Infections*
  • Coronavirus NL63, Human / genetics*
  • Coronavirus NL63, Human / isolation & purification
  • Genotype
  • Humans
  • Infant
  • Phylogeny
  • Respiratory Tract Infections / virology*

Grant support

This research was supported by grants from National Key Research and Development Program of China (2018YFC1200100 and 2016YFC1202701), National Science and Technology Major Project (2018ZX10301403-001-003 and 2018ZX10101002), National Natural Science Foundation of China (81702047, 81772191, 91842106 and 8181101118), Guangdong Provincial Department of Science and Technology (2018B020207013), the Thousand Talents Plan Award of China 2015 and State Key Laboratory of Respiratory Disease (SKLRD-QN-201715 and SKLRD-QN-201912), China Postdoctoral Science Foundation (2019T120722) and the PhD Start-up Fund of Natural Science Foundation of Guangdong Province, China, grants from the Nanshan Medical Development Foundation of Guangdong Province, National Key Technology R&D Program (2018YFC1311900), Guangdong Science and Technology Foundation (2019B030316028).