Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent ye...Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.展开更多
Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is l...Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is limited knowledge on the overall co-circulation of microorganisms in bats.Here,we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts.Among these,76 individual samples were selected for further metagenomics analysis.We found a complex microenvironment characterized by the general cocirculation of microbes from two different sources:mammal-associated viruses or environment-associated microbes.The later includes commensal bacteria,enterobacteria-related phages,and insect or fungal viruses of food origin.Results showed that 25%(19/76)of the samples contained at least one another mammal-associated virus,notably alphacoronaviruses(13/76)such as AlphaCoV/YN2012,HKU2-related CoV and AlphaCoV/Rf-HuB2013,along with viruses from other families.Notably,we observed three viruses co-circulating within a single bat,comprising two coronavirus species and one picornavirus.Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats.Furthermore,we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples,some of which formed new evolutionary lineages.Collectively,our study reveals the complex microenvironment of bat microbiome,facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.展开更多
Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses(CoVs) were detected in 50 of 951(positive rate 5.3%) intestinal specimens of eight bat speci...Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses(CoVs) were detected in 50 of 951(positive rate 5.3%) intestinal specimens of eight bat species collected in four provinces and the Tibet Autonomous Region of China by pan-coronavirus RT-PCR screening. Based on 400-nt RNA-dependent RNA polymerase(Rd RP) sequence analysis, eight belonged to genus Alphacoronavirus and 42 to Betacoronavirus.Among the 50 positive specimens, thirteen gave rise to CoV full-length Rd RP gene amplification for further sequence comparison, of which three divergent sequences(two from a unreported province) were subjected to full genome sequencing. Two complete genomes of betacoronaviruses(JTMC15 and JPDB144) and one nearly-complete genome of alphacoronavirus(JTAC2) were sequenced and their genomic organization predicted. The present study has identified additional numbers of genetically diverse bat-borne coronaviruses with a wide distribution in China. Two new species of bat CoV, identified through sequence comparison and phylogenetic analysis, are proposed.展开更多
基金funded by the National Natural Science Foundation of China(32102646)the Natural Science Foundation of Guangdong Province,China(2020A1515110315)+1 种基金the Start-up Research Project of Maoming Laboratory,China(2021TDQD002)the China Agriculture Research System of MOF and MARA(cars-35)。
文摘Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.
基金supported by the National Key R&D Program of China(2021YFC2300901 to P.Z.)China Natural Science Foundation for outstanding scholars(82325032 to P.Z.)+1 种基金the Self-Supporting Program of Guangzhou Laboratory(SRPG22-001 to P.Z.GZNL2023A01001 to ZLS).
文摘Bats are the natural reservoir hosts for SARS-related coronavirus(SARSr-CoV)and other highly pathogenic microorganisms.Therefore,it is conceivable that an individual bat may harbor multiple microbes.However,there is limited knowledge on the overall co-circulation of microorganisms in bats.Here,we conducted a 16-year monitoring of bat viruses in south and central China and identified 238 SARSr-CoV positive samples across nine bat species from ten provinces or administrative districts.Among these,76 individual samples were selected for further metagenomics analysis.We found a complex microenvironment characterized by the general cocirculation of microbes from two different sources:mammal-associated viruses or environment-associated microbes.The later includes commensal bacteria,enterobacteria-related phages,and insect or fungal viruses of food origin.Results showed that 25%(19/76)of the samples contained at least one another mammal-associated virus,notably alphacoronaviruses(13/76)such as AlphaCoV/YN2012,HKU2-related CoV and AlphaCoV/Rf-HuB2013,along with viruses from other families.Notably,we observed three viruses co-circulating within a single bat,comprising two coronavirus species and one picornavirus.Our analysis also revealed the potential presence of pathogenic bacteria or fungi in bats.Furthermore,we obtained 25 viral genomes from the 76 bat SARSr-CoV positive samples,some of which formed new evolutionary lineages.Collectively,our study reveals the complex microenvironment of bat microbiome,facilitating deeper investigations into their pathogenic potential and the likelihood of cross-species transmission.
基金supported by the Science and Technology Basic Work Program from the Ministry of Science and Technology of China(2013FY113600)NSFC-Yunnan Province Joint Fund(U1036601)Military Medical Health(13CXZ024)
文摘Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses(CoVs) were detected in 50 of 951(positive rate 5.3%) intestinal specimens of eight bat species collected in four provinces and the Tibet Autonomous Region of China by pan-coronavirus RT-PCR screening. Based on 400-nt RNA-dependent RNA polymerase(Rd RP) sequence analysis, eight belonged to genus Alphacoronavirus and 42 to Betacoronavirus.Among the 50 positive specimens, thirteen gave rise to CoV full-length Rd RP gene amplification for further sequence comparison, of which three divergent sequences(two from a unreported province) were subjected to full genome sequencing. Two complete genomes of betacoronaviruses(JTMC15 and JPDB144) and one nearly-complete genome of alphacoronavirus(JTAC2) were sequenced and their genomic organization predicted. The present study has identified additional numbers of genetically diverse bat-borne coronaviruses with a wide distribution in China. Two new species of bat CoV, identified through sequence comparison and phylogenetic analysis, are proposed.
