Apoptosis Enhances the Replication of Human Coronavirus OC43.

Sony Maharjan,Kyeongbin Baek,Younghee Lee,Minyoung Kim,Sangkyu Park,Dongbum Kim,Mijeong Kang,Hyung-Joo Kwon,Jinsoo Kim

doi:10.3390/v13112199

Sony Maharjan, Kyeongbin Baek + Show 7 more

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https://doi.org/10.3390/v13112199

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Journal: Viruses	Publication Date: Nov 1, 2021
Citations: 8	License type: CC BY 4.0

Affiliation: Hallym University, Chungbuk National University

Abstract

Human coronavirus OC43 (HCoV-OC43) is one of the coronaviruses causing a mild common cold, but few studies have been made on this strain. Here, we identified the molecular mechanisms involved in HCoV-OC43-induced apoptosis and its implications for viral reproduction in Vero cells and MRC-5 cells. HCoV-OC43 infection induced apoptosis that was accompanied by cleavage of caspase-3 and PARP, degradation of cyclin D1, and cell cycle arrest at S and G2M phases. Dephosphorylation of STAT1 and STAT3, induced by HCoV-OC43 infection, was also associated with HCoV-OC43-mediated apoptosis. The pan-caspase inhibitor effectively prevented HCoV-OC43-induced apoptosis and reduced viral replication, suggesting that apoptosis contributes to viral replication. Collectively our results indicate that HCoV-OC43 induces caspase-dependent apoptosis to promote viral replication in Vero cells and MRC-5 cells.

Highlights

Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses with a genome of approximately 26–32 kb
To determine the patterns of viral replication and the host response to infection, we used plaque assays (Figure 1A) and quantitative real-time PCR (Figure 1B) to measure HCoVOC43 in cell culture supernatants harvested at several times after inoculation of cells with
As we found that STAT1 and STAT3 dephosphorylation is associated with apoptosis and apoptosis contributes to virus replication, we investigated the effects of IFN-α-2a after human coronaviruses (HCoVs)-OC43 infection in Vero cells (Figure 6A and Figure S7)

Summary

Introduction

Coronaviruses (CoVs) are enveloped, positive-sense, single-stranded RNA viruses with a genome of approximately 26–32 kb. The endemic strains HCoV-OC43 and HCoV-229E were first reported in the 1960s, and two new strains, HCoV-NL63 and HCoV-HKU1, were identified in 2004 and 2005, respectively; these HCoVs are known to cause about 15–30% of cases of the common cold [2,3] The first instance of a dangerous CoV as a human pathogen was severe acute respiratory syndrome (SARS) in 2003 with a 9.6% mortality rate [4,5]. HCoV-OC43 is a strain that is frequently associated with upper respiratory tract infections and may exacerbate asthma and pneumonia [8,9] It is occasionally found with other pathologies such as meningitis and enteritis [10,11] and is associated with lower respiratory tract disease and acute disseminated encephalomyelitis in children [12,13,14]

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