Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enha...Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons under- lying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.展开更多
Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. The majority of ebolavirus species, most notably Zaire ebolavirus, can cause Ebola virus disease(EVD), formerly...Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. The majority of ebolavirus species, most notably Zaire ebolavirus, can cause Ebola virus disease(EVD), formerly known as Ebola hemorrhagic fever, in humans. EVD is associated with case-fatality rates as high as 90%, and there is currently no specific treatment or licensed vaccine available against EVD. Understanding the molecular biology and pathogenesis of ebolaviruses is important for the development of antiviral therapeutics. Ebolavirus encodes several forms of glycoproteins(GPs), which have some interesting characteristics, including the transcriptional editing coding strategy and extensive O-glycosylation modification, clustered in the mucin-like domain of GP1, full-length GP(GP_(1,2)), and shed GP. In addition to the canonical role of the spike protein, GP_(1,2), in viral entry, ebolavirus GPs appear to have multiple additional functions,likely contributing to the complex pathogenesis of the virus. Here, we review the roles of ebolavirus GPs in viral pathogenesis.展开更多
The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatali...The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.展开更多
Migration of infected animals and humans,and mutation are considered as the source of the introduction of new pathogens and strains into a country.In this paper,we formulate a mathematical model of Ebola virus disease...Migration of infected animals and humans,and mutation are considered as the source of the introduction of new pathogens and strains into a country.In this paper,we formulate a mathematical model of Ebola virus disease dynamics,that describes the introduction of a new strain of ebolavirus,through either mutation or immigration(which can be continuous or impulsive)of infectives.The mathematical analysis of the model shows that when the immigration of infectives is continuous,the new strain invades a country if its invasion reproduction number is greater than one.When the immigration is impulsive,a newly introduced strain is controllable when its reproduction number is less than the ratio of mortality to the population inflow and only locally stable equilibria exist.This ratio is one if the population size is constant.In case of mutation of the resident strain of ebolavirus,the coexistence of the resident and mutated strains is possible at least if their respective reproduction numbers are greater than one.Results indicate that the competition for the susceptible population is the immediate consequence of the coexistence of two different strains of ebolavirus in a country and this competition is favourable to the most infectious strain.Results also indicate that impulsive immigration of infectives when compared with continuous immigration of infectives gives time for the implementation of control measures.Our model results suggest controlled movements of people between countries that have had Ebola outbreaks despite the fact that closing boundaries is impossible.展开更多
In 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Za...In 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Approximately 30 years after the first epidemic, there is no vaccine or therapeutic medication approved to counter the Ebola virus. In this review, it emphasized that plant based antibodies can be an effective cure to Ebola hemorrhagic fever. Genetically modified Nicotiana benthamiana is used to manufacture ZMapp drug by Kentucky BioProcessing. ZMapp three-antibody cocktail binds to the Ebola virus to deactivate it and provides simulated immune response against sugar-tagged proteins on the outside of the Ebola virus, which had verified efficacy against Ebola infection in nonhuman primates and also successfully treated two American medical workers infected with Ebola virus disease.展开更多
文摘Ebolavirus can cause hemorrhagic fever in humans with a mortality rate of 50%-90%. Currently, no approved vaccines and antiviral therapies are available. Human TIM1 is considered as an attachment factor for EBOV, enhancing viral infection through interaction with PS located on the viral envelope. However, reasons under- lying the preferable usage of hTIM-1, but not other PS binding receptors by filovirus, remain unknown. We firstly demonstrated a direct interaction between hTIM-1 and EBOV GP in vitro and determined the crystal structures of the Ig V domains of hTIM-1 and hTIM-4. The binding region in hTIM-1 to EBOV GP was mapped by chimeras and mutation assays, which were designed based on structural analysis. Pseudovirion infection assays performed using hTIM-1 and its homologs as well as point mutants verified the location of the GP binding site and the importance of EBOV GP-hTIM-1 interaction in EBOV cellular entry.
基金supported by the National Natural Science Foundation of China (No. 31125003 and No. 31321001)the Basic Work Program of the Ministry of Science and Technology of China (2013FY113500)
文摘Ebolaviruses are highly dangerous pathogens exhibiting extreme virulence in humans and nonhuman primates. The majority of ebolavirus species, most notably Zaire ebolavirus, can cause Ebola virus disease(EVD), formerly known as Ebola hemorrhagic fever, in humans. EVD is associated with case-fatality rates as high as 90%, and there is currently no specific treatment or licensed vaccine available against EVD. Understanding the molecular biology and pathogenesis of ebolaviruses is important for the development of antiviral therapeutics. Ebolavirus encodes several forms of glycoproteins(GPs), which have some interesting characteristics, including the transcriptional editing coding strategy and extensive O-glycosylation modification, clustered in the mucin-like domain of GP1, full-length GP(GP_(1,2)), and shed GP. In addition to the canonical role of the spike protein, GP_(1,2), in viral entry, ebolavirus GPs appear to have multiple additional functions,likely contributing to the complex pathogenesis of the virus. Here, we review the roles of ebolavirus GPs in viral pathogenesis.
基金supported by the Public Health Agency of Canada(PHAC)partially supported by the NIH and CIHR grants to X.G.Qiu(U19 AI109762-1 and CIHR-IER-143487,respectively)+1 种基金the National Natural Science Foundation of China International Cooperation and Exchange Program(8161101193)National Science and Technology Major Project(2016ZX10004222)to G.Wong
文摘The family Filoviridae, which includes the genera Marburgvirus and Ebolavirus, contains some of the most pathogenic viruses in humans and non-human primates (NHPs), causing severe hemorrhagic fevers with high fatality rates. Small animal models against filoviruses using mice, guinea pigs, hamsters, and ferrets have been developed with the goal of screening candidate vaccines and antivirals, before testing in the gold standard NHP models. In this review, we summarize the different animal models used to understand filovirus pathogenesis, and discuss the advantages and disadvantages of each model with respect to filovirus disease research.
文摘Migration of infected animals and humans,and mutation are considered as the source of the introduction of new pathogens and strains into a country.In this paper,we formulate a mathematical model of Ebola virus disease dynamics,that describes the introduction of a new strain of ebolavirus,through either mutation or immigration(which can be continuous or impulsive)of infectives.The mathematical analysis of the model shows that when the immigration of infectives is continuous,the new strain invades a country if its invasion reproduction number is greater than one.When the immigration is impulsive,a newly introduced strain is controllable when its reproduction number is less than the ratio of mortality to the population inflow and only locally stable equilibria exist.This ratio is one if the population size is constant.In case of mutation of the resident strain of ebolavirus,the coexistence of the resident and mutated strains is possible at least if their respective reproduction numbers are greater than one.Results indicate that the competition for the susceptible population is the immediate consequence of the coexistence of two different strains of ebolavirus in a country and this competition is favourable to the most infectious strain.Results also indicate that impulsive immigration of infectives when compared with continuous immigration of infectives gives time for the implementation of control measures.Our model results suggest controlled movements of people between countries that have had Ebola outbreaks despite the fact that closing boundaries is impossible.
文摘In 2014, the World Health Organization was notified of an outbreak of a communicable disease characterized by fever, severe diarrhea, vomiting, and a high fatality rate in Guinea. Virologic investigation identified Zaire ebolavirus (EBOV) as the causative agent. Approximately 30 years after the first epidemic, there is no vaccine or therapeutic medication approved to counter the Ebola virus. In this review, it emphasized that plant based antibodies can be an effective cure to Ebola hemorrhagic fever. Genetically modified Nicotiana benthamiana is used to manufacture ZMapp drug by Kentucky BioProcessing. ZMapp three-antibody cocktail binds to the Ebola virus to deactivate it and provides simulated immune response against sugar-tagged proteins on the outside of the Ebola virus, which had verified efficacy against Ebola infection in nonhuman primates and also successfully treated two American medical workers infected with Ebola virus disease.