Bats are a natural reservoir host and source of infection for several microorganisms, including several zoonotic viruses that can cause severe human diseases. Some zoonotic viruses associated with bats have been identified, including pathogens that can cause severe human diseases such as Ebola, Marb...
Bats are a natural reservoir host and source of infection for several microorganisms, including several zoonotic viruses that can cause severe human diseases. Some zoonotic viruses associated with bats have been identified, including pathogens that can cause severe human diseases such as Ebola, Marburg, Nipah, and recently SARS-CoV-2. In the present study, faecal samples were collected from the bat habitats at different geographical locations in South Korea between 2016 and 2021. The present study aimed to identify the genetic characteristics of viruses circulating in bats in South Korea and to study their evolution. Besides, nucleoside-modified mRNA was designed for an mRNA-based vaccine platform against potential zoonotic virus.
I have conducted the long-term surveillance of RNA viruses on Korean bats by RT-PCR specific for virus families, including Coronaviridae, Paramyxoviridae, Flaviviridae, Filoviridae, Rhaboviridae, Mammalian orthoreovirus, and Influenza A. Coronaviruses, Paramyxoviruses, Flavivirus, and Reoviruses were detected in bat faeces. Based on the data investigated between 2016 and 2019: Seventy-eight samples were positive for coronaviruses (15.2%). The positive rates tended to increase during the awakening-(April) period. Alphacoronavirus were detected in 7 bat species, whereas Betacoronaviruses were only found in Rhinolophus ferrumequinum. Those Betacoronaviruses were related to SARS- and MERS-related CoVs identified in China and South Korea, respectively. In contrast, Alphacoronaviruses had higher genetic diversity and had a broader distribution in Korea. The diverse coronaviruses in Korean bats are likely to undergo cross-species transmission events due to the richness of host species.
On the other hand, I report a newly discovered MRV type 1 detected in Miniopterus schreibersii that may have resulted from reassortment events. Using next-generation sequencing RNA-sequencing (RNA-seq), I found that the ratios of the relative abundances of RNA levels of the ten reovirus segments are constant during the late stages of infection in infected cells. Remarkably, the relative abundances of the total RNA of M2 (coding µ1 protein) and S4 (coding 3 protein) genes were higher than others throughout the infection periods. Additionally, massive junctions were defined.
To understand the features of the genomic bat coronavirus representatives and their relationships, I utilized the RNA-seq approach to complete genomic sequences of bat coronaviruses. Six full-length genomes representing newly identified bat coronaviruses in South Korea were obtained. Based on genome structure, conserved replicase domains, spike gene, and nucleocapsid genes, the analysis revealed that bat Alphacoronaviruses were from three different viral species. Among them, the newly identified B20-97 strain may represent a new putative species closely related to PEDV. In addition, the newly-identified MERS-related coronavirus exhibited shared genomic nucleotide identities of less than 76.4% with other Merbecoviruses. Recombination analysis and multiple alignments of spike and RBD amino acid sequences suggested that this strain underwent recombination events and could possibly use hDPP4 molecules as its receptor. The bat SARS-related CoV B20-50 is unlikely to be able to use hACE2 as its receptor and lacks an open reading frame in the ORF8 gene region. The evolution of the bat coronaviruses-related ORF8 accessory gene is also discussed.
Finally, due to the emergence or re-emergence of coronavirus outbreaks, I attempted to build the first step of the mRNA vaccine platform for potential emerging coronavirus. The targeting of some mRNA template candidates showed high expression in vitro. I designed nucleoside-modified mRNA vaccines encoding the spike and nucleocapsid genes of SARS-CoV-2 and the spike gene of bat SARS-related CoV. The mRNAs were formulated with lipid nanoparticles. Unfortunately, the vaccination of mice showed low efficient immunogenicity due to inefficient in vivo delivery.
These findings lead us to believe that further studies are needed to understand the diversity and evolution of coronavirus and other viruses in bats. In addition, the mRNA vaccine platform should be comprehensive for preparedness for future emerging diseases.
Bats are a natural reservoir host and source of infection for several microorganisms, including several zoonotic viruses that can cause severe human diseases. Some zoonotic viruses associated with bats have been identified, including pathogens that can cause severe human diseases such as Ebola, Marburg, Nipah, and recently SARS-CoV-2. In the present study, faecal samples were collected from the bat habitats at different geographical locations in South Korea between 2016 and 2021. The present study aimed to identify the genetic characteristics of viruses circulating in bats in South Korea and to study their evolution. Besides, nucleoside-modified mRNA was designed for an mRNA-based vaccine platform against potential zoonotic virus.
I have conducted the long-term surveillance of RNA viruses on Korean bats by RT-PCR specific for virus families, including Coronaviridae, Paramyxoviridae, Flaviviridae, Filoviridae, Rhaboviridae, Mammalian orthoreovirus, and Influenza A. Coronaviruses, Paramyxoviruses, Flavivirus, and Reoviruses were detected in bat faeces. Based on the data investigated between 2016 and 2019: Seventy-eight samples were positive for coronaviruses (15.2%). The positive rates tended to increase during the awakening-(April) period. Alphacoronavirus were detected in 7 bat species, whereas Betacoronaviruses were only found in Rhinolophus ferrumequinum. Those Betacoronaviruses were related to SARS- and MERS-related CoVs identified in China and South Korea, respectively. In contrast, Alphacoronaviruses had higher genetic diversity and had a broader distribution in Korea. The diverse coronaviruses in Korean bats are likely to undergo cross-species transmission events due to the richness of host species.
On the other hand, I report a newly discovered MRV type 1 detected in Miniopterus schreibersii that may have resulted from reassortment events. Using next-generation sequencing RNA-sequencing (RNA-seq), I found that the ratios of the relative abundances of RNA levels of the ten reovirus segments are constant during the late stages of infection in infected cells. Remarkably, the relative abundances of the total RNA of M2 (coding µ1 protein) and S4 (coding 3 protein) genes were higher than others throughout the infection periods. Additionally, massive junctions were defined.
To understand the features of the genomic bat coronavirus representatives and their relationships, I utilized the RNA-seq approach to complete genomic sequences of bat coronaviruses. Six full-length genomes representing newly identified bat coronaviruses in South Korea were obtained. Based on genome structure, conserved replicase domains, spike gene, and nucleocapsid genes, the analysis revealed that bat Alphacoronaviruses were from three different viral species. Among them, the newly identified B20-97 strain may represent a new putative species closely related to PEDV. In addition, the newly-identified MERS-related coronavirus exhibited shared genomic nucleotide identities of less than 76.4% with other Merbecoviruses. Recombination analysis and multiple alignments of spike and RBD amino acid sequences suggested that this strain underwent recombination events and could possibly use hDPP4 molecules as its receptor. The bat SARS-related CoV B20-50 is unlikely to be able to use hACE2 as its receptor and lacks an open reading frame in the ORF8 gene region. The evolution of the bat coronaviruses-related ORF8 accessory gene is also discussed.
Finally, due to the emergence or re-emergence of coronavirus outbreaks, I attempted to build the first step of the mRNA vaccine platform for potential emerging coronavirus. The targeting of some mRNA template candidates showed high expression in vitro. I designed nucleoside-modified mRNA vaccines encoding the spike and nucleocapsid genes of SARS-CoV-2 and the spike gene of bat SARS-related CoV. The mRNAs were formulated with lipid nanoparticles. Unfortunately, the vaccination of mice showed low efficient immunogenicity due to inefficient in vivo delivery.
These findings lead us to believe that further studies are needed to understand the diversity and evolution of coronavirus and other viruses in bats. In addition, the mRNA vaccine platform should be comprehensive for preparedness for future emerging diseases.
주제어
#zoonotic bat-borne viruses Coronavirus Reovirus RNA-base vaccine Korea
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