Genetic variability of human coronavirus OC43-, 229E-, and NL63-like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients

Abstract

In the winter-spring seasons 2003-2004 and 2004-2005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E-, NL63-, and OC43-like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT-PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type-specific primers targeting genes 1ab and N. The HuH-7 cell line was found to be susceptible to isolation and identification of OC43- and 229E-like strains. Overall, hCoV infection was caused by OC43-like, 229E-like, and NL63-like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63-like strains were not found to circulate in 2003-2004, and 229E-like strains did not circulate in 2004-2005, while OC43-like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection.

Rat respiratory coronavirus infection: replication in airway and alveolar epithelial cells and the innate immune response

“…Although several animal model systems have been used for investigation of SARS-CoV infections (Subbarao & Roberts, 2006), good animal models are not available for the other four human CoVs (229E, OC43, NL63 and HKU1). Although these four human CoVs typically infect the upper respiratory tract, they are also known to infect the lower respiratory tract, especially in infants, elderly and immunocompromised patients (Gerna et al, 2006;Kahn, 2006). However, the MHV-1 strain of murine CoV is being used as an animal model for respiratory CoV infection in A/J mice (De Albuquerque et al, 2006;Khanolkar et al, 2009).…”

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

“…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).…”

Detection of Human Herpesvirus-7 DNA in Bronchoalveolar Lavage

“…Automated total nucleic acid extraction was performed with Nuclisens EasyMAG platform (bioMérieux, Marcy l'Etoile, France), according to the manufacturer's instructions. Qualitative detection of nucleic acid of human metapneumovirus [9] , bocaviruses [10] , and coronaviruses [11] was performed as previously described, as well as TaqMan real-time PCR for HHV-6 [12] , enteroviruses [13] , rhinoviruses [14] , parainfluenza viruses [15] , and influenza A and B viruses [16] . For the detection of HCMV-DNA and EBV-DNA, two TaqMan real-time PCR assays were used utilizing commercial kits (Q-CMV Real-Time Complete Kit, Q-EBV, Nanogen Advanced Diagnostics, Milan, Italy), according to the manufacturer's instructions.…”