Characterization of infection and replication of human coronavirus NL63 in vitro as a surrogate for SARS-CoV-2
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Date
2021-12
Authors
Castillo Vilca, Gino
Major Professor
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Gimenez Lirola, Luis
Roth, James Allen
Gauger, Phillip C
Nelli, Rahul
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Abstract
HCoV-NL63 is predominantly associated with respiratory disease, particularly with upper and lower respiratory tract infections in children. Mild respiratory symptoms include fever, rhinorrhea, pharyngitis, cough, and sore throat, while more serious lower respiratory tract symptoms are croup, bronchitis, and/or bronchiolitis. Nevertheless, syndromic diagnosis of HCoV-NL63-associated disease is difficult because it relies on clinical symptoms, which are non-specific and overlap with those commonly reported in other viruses and bacteria respiratory infections. For instance, there are at least seven coronaviruses capable of infecting humans, including HCoV-NL63. The Alphacoronavirus HCoV-229E, and the Betacoronavirus members HCoV-OC43 and HCoV-HKU1, have been associated with mild to asymptomatic respiratory infections in the upper respiratory tract. In addition, the Betacoronavirus members, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the recently discovered SARS-CoV-2, can cause lower respiratory tract infections and more severe disease, particularly pneumonia, leading to fatal consequences in many cases. However, recent clinical reports showed that new emerging strains of HCoV-NL63 are also developing severe diseases.
This thesis reviewed the current HCoV-NL63-related research and provide important highlights about the current circulating HCoV-NL63 clades and its life cycle. Our results showed higher susceptibility to HCoV-NL63 infection in LLC-MK2 cells followed by ALI-HREC, with very low susceptibility and no significant virus replication in HREC monolayer cultures. Moreover, the susceptibility of these different cultures to HCoV-NL63 was associated with differences in the expression levels of ACE2 receptor protein across cultures. Interestingly, we found that SARS-CoV-2 were able to infect this HREC monolayer, besides their low ACE2 expression, which would correlate with the cumulative epidemiological evidence on the differences in their transmissibility. This study further justified the development of alternative culture models toward the development of therapeutic interventions against re-emerging coronaviruses.
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thesis