Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that ca...Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, C?te d'Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.展开更多
Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately95% of the patients appear sig...Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately95% of the patients appear signs within 21 d after exposure. Typical features include fever,profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred.Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer(four-fold) contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a "cocktail"of humanized-mouse antibodies(ZMapp), recombinant inhibitor of factor VIIa/tissue factor,activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.展开更多
Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV posses...Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.展开更多
基金Supported by Department of Science and Technology-Science and Engineering Research Board(DST-SERB),New Delhi,India
文摘Ebola virus disease is one of the most deadly ailments known to mankind due to its high mortality rate(up to 90%) accompanying with the disease. Ebola haemorrhagic fever(EHF) is an infectious disease of animal that can be transmitted to both human and non-human primates. The first epidemic of EHF occurred in 1976 in the Democratic Republic of the Congo. The incubation period of ebola is less than 21 days. Ebola virus infections are depicted by immune suppression and a systemic inflammatory response that leads to damage of the vascular, coagulation and immune systems, causing multi-organ failure and shock. Five genetically distinct members of the Filoviridae family responsible for EHF are as follows: Zaire ebolavirus, Sudan ebolavirus, C?te d'Ivoire ebolavirus, Bundibugyo ebolavirus and Reston ebolavirus. The ongoing 2014 West Africa ebola epidemic has been considered as the most serious panic in the medical field with respect to both the number of human cases and death toll. The natural host for ebola virus is unknown, thus it is not possible to carry out programs to regulate or abolish virus from transmission to people. The ebola virus infection provides little chance to develop acquired immunity causing rapid progression of the disease. It is pertinent to mention that at present, there is no antiviral therapy or vaccine that is helpful against ebola virus infection in humans. The impediment of EHF necessitates much better understanding of the epidemiology of the disease, particularly the role of wildlife, as well as bats, in the spread of ebola virus to humans.
基金Supported by Iranian Research Center for HIV/AIDS(IRCHA)affiliated to Tehran University of Medical Sciences(Grant No.93-2-12)
文摘Ebola virus is transmitted to people as a result of direct contact with body fluids containing virus of an infected patient. The incubation period usually lasts 5 to 7 d and approximately95% of the patients appear signs within 21 d after exposure. Typical features include fever,profound weakness, diarrhea, abdominal pain, cramping, nausea and vomiting for 3-5days and maybe persisting for up to a week. Laboratory complications including elevated aminotransferase levels, marked lymphocytopenia, and thrombocytopenia may have occurred.Hemorrhagic fever occurs in less than half of patients and it takes place most commonly in the gastrointestinal tract. The symptoms progress over the time and patients suffer from dehydration, stupor, confusion, hypotension, multi-organ failure, leading to fulminant shock and eventually death. The most general assays used for antibody detection are direct IgG and IgM ELISAs and IgM capture ELISA. An IgM or rising IgG titer(four-fold) contributes to strong presumptive diagnosis. Currently neither a licensed vaccine nor an approved treatment is available for human use. Passive transfer of serum collected from survivors of Junin virus or Lassa virus, equine IgG product from horses hypervaccinated with Ebola virus, a "cocktail"of humanized-mouse antibodies(ZMapp), recombinant inhibitor of factor VIIa/tissue factor,activated protein C, RNA-polymerase inhibitors and small interfering RNA nano particles are among the therapies in development. Preclinical evaluation is also underway for various vaccine candidates. One is a chimpanzee adenovirus vector vaccine; other vaccines involve replication-defective adenovirus serotype 5 and recombinant vesicular stomatitis virus.
文摘Ebola virus （EBOV） is a key member of Filoviridae family and causes severe human infectious diseases with high morbidity and mortality. As a typical negative-sense single-stranded RNA （-ssRNA） viruses, EBOV possess a nucleocapsid protein （NP） to facilitate genomic RNA encapsidation to form viral ribonucleoprotein complex （RNP） together with genome RNA and polymerase, which plays the most essential role in virus proliferation cycle. However, the mechanism of EBOV RNP formation remains unclear. In this work, we solved the high resolution structure of core domain of EBOV NP. The polypeptide of EBOV NP core domain （NPcore） pos- sesses an N-lobe and C-lobe to clamp a RNA binding groove, presenting similarities with the structures of the other reported viral NPs encoded by the members from Mononegavirales order. Most strikingly, a hydrophobic pocket at the surface of the C-lobe is occupied by an a- helix of EBOV NPcore itself, which is highly conserved among filoviridae family. Combined with other bio- chemical and biophysical evidences, our results provides great potential for understanding the mechanism underlying EBOV RNP formation via the mobility of EBOV NP element and enables the development of antiviral therapies targeting EBOV RNP formation.
