PMC:7103735 / 4638-10601 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7103735","sourcedb":"PMC","sourceid":"7103735","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7103735","text":"Discovery of HCoVs\nAvian infectious bronchitis virus was the first CoV isolated in 1930. Different CoVs were subsequently isolated in infected rodents and domestic animals, including mouse, pig, cow, turkey, cats, and dogs. CoVs were once believed not to cause human disease, but this was changed after the successful isolation of HCoV strain B814 from the clinical specimen of patients with common cold by serial passage of inoculum in tracheal organ culture in 1962 [2]. In the 1960s, several novel HCoVs were described but no further characterization was performed in most cases [3,4]. 229E and OC43 were known as causative agents of the common cold and upper respiratory tract infection, accounting for up to 30% of cases with common cold [4]. 229E is a prototype strain isolated using tracheal organ culture. OC43 was isolated from organ culture and subsequent serial passage in the brain of suckling mice. The clinical features of 229E and OC43 infection were characterized in human volunteer study [4]. In most cases, natural infection with HCoVs results in mild common cold-like symptoms. Severe lower respiratory tract infection develops only in immunocompromised patients [5]. Apart from a respiratory infection, 229E and OC43 were suspected to infect the central nervous system (CNS) as mRNA and CoV-like particles were detected in CNS samples of patients with multiple sclerosis. This claim was further supported by the susceptibility of human neural primary culture to 229E and OC43 [6]. However, the influence of 229E and OC43 on the development and progression of multiple sclerosis awaits further investigations.\nIn the pre-SARS era, it was generally accepted that HCoVs cause mild respiratory disease only. This concept was changed after the emergence of SARS-CoV. The first reported case of SARS-CoV infection was retrospectively dated back to November 2002 in Guangdong Province of China. In the subsequent seven months, the SARS epidemic resulted in over 8000 reported cases in 37 countries with a case fatality of 9.6% [7]. The superspreading events in SARS-CoV transmission caused fears in the society. Although the exact cause of superspreading remains to be understood, the host but not the virus only is thought to play a key role in the release of large amounts of virions in superspreading. In this regard, the use of immunosuppressive agents such as high-dose steroid in an early phase of viral infection as a treatment modality might boost viral replication leading to the shedding of large amounts of virus. Likewise, the immunocompromised status of the superspreader could have the same effect. In addition, mutation of virus susceptibility genes encoding restriction factors implicated in host antiviral defence would also result in the shedding of extraordinarily large quantities of the virus [8]. In other words, compromising host antiviral defence or decoupling host antiviral immune response from viral replication might allow or facilitate superspreading.\nSARS-CoV was isolated and identified as the causative agent of SARS [9]. Unlike 229E and OC43, SARS-CoV infection causes lower respiratory tract infection, accompanied by a cytokine storm in patients with poor outcome. Life-threatening ARDS was developed in some critically ill patients. Apart from a respiratory infection, gastrointestinal and CNS infection was also found in some patients with SARS [10,11]. FRHK4 and Vero-E6 cells played an important role in the discovery of SARS-CoV [9]. The same as chicken embryos in which other CoVs including avian infectious bronchitis virus were isolated and cultured, these cells are highly susceptible to SARS-CoV infection because they are type I interferon-defective [12]. Consistent with this, infection of STAT1−/− mice with SARS-CoV resulted in a lethal outcome with a profibrotic phenotype in the lung [13]. These mice cannot clear the virus. All these highlight the importance of host antiviral response in the control of SARS-CoV infection at the cellular and organismal level.\nIn the post-SARS era, CoV research was brought back to the limelight and more effort was put into the search for novel HCoVs. The search was fruitful and two new HCoVs were identified in human samples positive for HCoV but not for SARS-CoV. NL63 and HKU1 were first isolated from a child suffering from bronchiolitis and a patient with pneumonia, respectively [14,15]. HKU1 is difficult to culture and can only be propagated in primary human airway epithelial cells cultured at the air–liquid interface. Similar to 229E and OC43, NL63 and HKU1 were found worldwide, causing mild respiratory diseases. Particularly, NL63 infection was associated with virus-induced croup in children [16]. All these four viruses are community-acquired HCoVs that are well adapted to humans. Only in rare cases, they might be accidentally mutated to cause more severe lower respiratory tract disease. For example, a subtype of NL63 was recently found to be associated with severe lower respiratory tract infection in China [17].\nAnother highly pathogenic HCoV outbreak emerged in 2012 from Saudi Arabia. A new HCoV subsequently named MERS-CoV was isolated from patients who developed acute pneumonia and renal failure [18]. Exported MERS cases were also reported outside Arabian Peninsula occasionally. One relatively big secondary outbreak with 186 confirmed cases occurred in South Korea in 2015. Up to January 2020, \u003e2500 laboratory-confirmed case were reported with a case fatality of 34.4%. Clinical symptoms were diverse in MERS patients, ranging from asymptomatic to ARDS [19]. Acute renal injury was unique in MERS patients, but it is more commonly observed in the Middle East than in South Korea. MERS-CoV replicates well in many different types of cells and extrapulmonary tissues including the kidney and intestinal tract [20,21]. MERS-CoV is endemic in Arabian Peninsula with sporadic, but recurrent outbreaks occurring continuously since 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