Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, w...Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.展开更多
With the rapid growth in the number of passenger cars(PCs)in China over the past decades,more than ten million tons of used tires have already become solid wastes and subsequently caused serious environmental issues.D...With the rapid growth in the number of passenger cars(PCs)in China over the past decades,more than ten million tons of used tires have already become solid wastes and subsequently caused serious environmental issues.Due to the presence of synthetic rubber in PC tires,waste PC tires cannot be disposed through rubber reclaiming technology.Thus,waste PC tires have become one of fastest growing solid wastes in China.First,the current disposal capacity of the pyrolysis method,regarded as a promising technology for the disposal of waste PC tires,is surveyed and compared with other disposal methods mentioned in previous papers.Second,this work establishes a model to predict the total number of waste PC tires in the next five years depending on the rate of PC growth and current waste tire disposal capacity.Moreover,pyrolysis is evaluated on 15 collected waste PC tires selected from the most representative tire brands in the Chinese market.The corresponding results imply that~68.5%of S was into oil and~44.3%N and large amount of heavy metals resided in solid carbon which severely limit further applications.Finally,a new pyrolysis technology is introduced that may represent a solution to the limits in the application of tire disposal methods and relief for the coming waste tire crisis.展开更多
基金These authors contributed equally to this work. We thank Drs S Vaidya and E Chow （University of California Los Angeles, USA） for their help in setting up critical experimental systems. We greatly thank Dr K Holmes （University of Colorado Health Sciences Center, USA） for sharing with us 17C1-1 cell line and helping to optimize the protocol to produce high titered MHV-A59 virus stock. We also thank Drs R Baric and L Su （University of North Carolina, USA） for the gift of MHV-A59 and guidance of virus infection. We thank Dr K Lim （National Neuroscience Institute, Singapore） for the gift of Ubi plasmids. We thank Dr M Wathelet （University of Cincinnati College of Medicine, USA） for sharing the nsp3 construct. Also we thank Dr G Gao （Institute of Biophysics, CAS） for providing us with VSV. This research was partly supported by grants from the National Natural Science Foundation of China （30728006） to Genhong Cheng and the National Basic Research Program of MOST （2004BA519A61, 2006CB504300, 2007DFC30190） to Hong Tang.
文摘Infections by coronaviruses such as severe acute respiratory syndrome （SARS） coronavirus （SCoV） and mouse hepatitis virus A59 （MHV-A59） result in very little type I interferon （IFN） production by host cells, which is potentially responsible for the rapid viral growth and severe immunopathology associated with SARS. However, the molecular mechanisms for the low IFN production in cells infected with coronaviruses remain unclear. Here, we provide evidence that Papain-like protease domain 2 （PLP2）, a catalytic domain of the nonstructural protein 3 （nsp3） of MHV-A59, can bind to IRF3, cause its deubiquitination and prevent its nuclear translocation. As a consequence, co-expression of PLP2 strongly inhibits CARDIF-, TBK1- and IRF3-mediated IFNp reporter activities. In addition, we show that wild-type PLP2 but not the mutant PLP2 lacking the deubiquitinase （DUB） activity can reduce IFN induction and promote viral growth in cells infected with VSV. Thus, our study uncovered a viral DUB which coronaviruses may use to escape from the host innate antiviral responses.
基金support of the National Key R&D Program of China[Grant No.2018YFC1902601].
文摘With the rapid growth in the number of passenger cars(PCs)in China over the past decades,more than ten million tons of used tires have already become solid wastes and subsequently caused serious environmental issues.Due to the presence of synthetic rubber in PC tires,waste PC tires cannot be disposed through rubber reclaiming technology.Thus,waste PC tires have become one of fastest growing solid wastes in China.First,the current disposal capacity of the pyrolysis method,regarded as a promising technology for the disposal of waste PC tires,is surveyed and compared with other disposal methods mentioned in previous papers.Second,this work establishes a model to predict the total number of waste PC tires in the next five years depending on the rate of PC growth and current waste tire disposal capacity.Moreover,pyrolysis is evaluated on 15 collected waste PC tires selected from the most representative tire brands in the Chinese market.The corresponding results imply that~68.5%of S was into oil and~44.3%N and large amount of heavy metals resided in solid carbon which severely limit further applications.Finally,a new pyrolysis technology is introduced that may represent a solution to the limits in the application of tire disposal methods and relief for the coming waste tire crisis.
