(2)
Ebola...always watching, always waiting
Keeping you informed with up-to-date news
Transmission
From Animals: Ebola is transmitted to humans from undetermined animal origins. In central Africa and southern Asia, the virus is known to circulate through animals, but they may or may not show any signs of being infected. For all cases, the animals serve as reservoirs for Eboloa and infect humans through direct contact. No nonhuman vertebrate hosts or arthropod vectors have been determined as the natural hosts for certain. With Ebola-Reston, there was an infection within a colony of Asian monkeys that may test that idea. On the other hand, the Sudan and Zaire Ebola species are pathogenic for monkeys and apes which leans towards saying they are not reservoirs, but are secondary hosts, like humans.
Fruit-eating and insect-eating bats have been recently shown to support replication and circulation of high Ebola titers. The catch? They aren't getting sick! Bats have previously been suspected for the outbreaks in Sudan. These furry, flying creatures could be the reason why Ebola still survives in nature.
From Humans: Outbreaks usually start with one infected person which then spreads as secondary and subsequent infections to family members, close acquaintances, and medical/nursing staff. Ebola epidemics ends because the transmission of infection is short-lived. Physical contact is necessary between humans and if you are involved in nursing or preparing bodies for burial, you may be in trouble because there is an increased risk of exposure. Outbreaks during 1976 and 1995 occured because of transmission inside hospitals because of contaminated syringes and needles. Transmission has a secondary infection rate of 12% at its highest. Burials in Uganda now deal with the virus in dead bodies by spraying down the burial site with chlorine.
What to Avoid: Blood, secretions, excretions, semen, and other body fluids from the infected. Experimentally infected and quarantined imported monkeys have been shown to transmit the virus via droplets and aerosols and virus particles have been found within the lungs. Fortunately, there are very low chances of Ebola spreading in human outbreaks via aerosolized particles.
Fruit-eating and insect-eating bats have been recently shown to support replication and circulation of high Ebola titers. The catch? They aren't getting sick! Bats have previously been suspected for the outbreaks in Sudan. These furry, flying creatures could be the reason why Ebola still survives in nature.
From Humans: Outbreaks usually start with one infected person which then spreads as secondary and subsequent infections to family members, close acquaintances, and medical/nursing staff. Ebola epidemics ends because the transmission of infection is short-lived. Physical contact is necessary between humans and if you are involved in nursing or preparing bodies for burial, you may be in trouble because there is an increased risk of exposure. Outbreaks during 1976 and 1995 occured because of transmission inside hospitals because of contaminated syringes and needles. Transmission has a secondary infection rate of 12% at its highest. Burials in Uganda now deal with the virus in dead bodies by spraying down the burial site with chlorine.
What to Avoid: Blood, secretions, excretions, semen, and other body fluids from the infected. Experimentally infected and quarantined imported monkeys have been shown to transmit the virus via droplets and aerosols and virus particles have been found within the lungs. Fortunately, there are very low chances of Ebola spreading in human outbreaks via aerosolized particles.
Map of Philippines where Ebola Reston monkeys came from (7)
Map of African outbreaks of Ebola (5)
Symptoms...not fun
Hemorrhagic fever, generalized internal bleeding, liver damage and dysfunction, disseminated intravascular coagulation (systemic clotting of the blood that can be caused by activated neutrophils), drop in white blood cell counts, secondary bacterial infections in bloodstream, and shock to due decrease in blood volume which leads to decrease in blood pressure.
In the beginning of the infection, there will quickly be fever, chills, headache, muscle pain, and no desire to eat. Soon, the patient will experience abdomianl pain, sore throat, nausea, vomiting, cough, joint pain, and diarrhea. Symptoms that are different from other viral hemorrhagic fevers because they are more severe in Ebola are prostration, lethargy, wasting, and diarrhea.
Check patients for dehydration, apathy, disorientation, and specific rash with peeling skin around days 5-7 of illness. There will be bleeding in the GI tract and localized skin hemorrhages and from puncture wounds and mucous membrane. If non-fatal, fever will develop and stay approximately 5-9 days while fatal cases have signs in much earlier stages and death will follow between days 6-16 after hemorrhaging and shock.
While shock occurs because of drop in blood volume, the release of cytokines also contributes because of the increase in endothelial permeability.
When fatal, studies have shown there to be high titers of virus in the body and no or very little effective immune system response. Ebola can create immunosuppression in patients which lends to the severity and spread.
In the beginning of the infection, there will quickly be fever, chills, headache, muscle pain, and no desire to eat. Soon, the patient will experience abdomianl pain, sore throat, nausea, vomiting, cough, joint pain, and diarrhea. Symptoms that are different from other viral hemorrhagic fevers because they are more severe in Ebola are prostration, lethargy, wasting, and diarrhea.
Check patients for dehydration, apathy, disorientation, and specific rash with peeling skin around days 5-7 of illness. There will be bleeding in the GI tract and localized skin hemorrhages and from puncture wounds and mucous membrane. If non-fatal, fever will develop and stay approximately 5-9 days while fatal cases have signs in much earlier stages and death will follow between days 6-16 after hemorrhaging and shock.
While shock occurs because of drop in blood volume, the release of cytokines also contributes because of the increase in endothelial permeability.
When fatal, studies have shown there to be high titers of virus in the body and no or very little effective immune system response. Ebola can create immunosuppression in patients which lends to the severity and spread.
Photograph of Ebola rash (4)
Infirmary in Africa (7)
Treatment...just in case
What to do with patients: Isolation is crucial as well as protecting an medical/nursing staff. To do this, there needs to be strict barrier nursing techniques and HEPA-filtered (High Efficiency Particulate Air) respirators to filter out any aerosolized particles from the patient. Interferons and Ribavirin that would otherwise be used against other viruses that cause viral hemorrhagic fever, have no effect on Ebola. Continue to rehydrate patients with intravenous fluids as they become dehydrated.
Vaccine: First Ebola virus vaccine for nonhuman primates was based on injecting DNA plasmids that coded for glycoprotein and nucleoprotein, followed with boosting with an adenovirus recombinant vector expressing glycoprotein. This needed several months for immunity to develop. Even though it was possible to accelerate protection, previous immunity to adenovirus within humans may limit how well this vaccine will work. In 2005, an Ebola vaccine was created with live attenuated recombinant strains of vesicular stomatitis virus (cattle rhabdovirus) that expressed Ebola glycoproteins. When cynomolgus monkeys were vaccinated, they had total protection when exposed to lethal Ebola.
Vaccine: First Ebola virus vaccine for nonhuman primates was based on injecting DNA plasmids that coded for glycoprotein and nucleoprotein, followed with boosting with an adenovirus recombinant vector expressing glycoprotein. This needed several months for immunity to develop. Even though it was possible to accelerate protection, previous immunity to adenovirus within humans may limit how well this vaccine will work. In 2005, an Ebola vaccine was created with live attenuated recombinant strains of vesicular stomatitis virus (cattle rhabdovirus) that expressed Ebola glycoproteins. When cynomolgus monkeys were vaccinated, they had total protection when exposed to lethal Ebola.
Protein Map of Ebola Virus RNA (2)
You know you want to learn about my genome
The genome consists of seven genes. The nucleocapsid protein is located near the 3’ end and the RNA polymerase gene is near the 5’ end. Genes are flanked by conserved sequences that signal transcription termination, polyadenylation, and transcription reinitiation. The stop and start sites are overlapping by 20 nucleotides, this causes the 3’ end of one mRNA to lie downstream from the 5’ end of the next mRNA. The role of this overlap is not fully understood, but it is speculated that it may control the level of initiation of synthesis of mRNA of the downstream genes. Each gene codes for one protein that is packaged within a virion (GP an exception):
Nucleoprotein (NP) is a highly phosphorylated protein that forms the helical nucleocapid.
Virus protein (VP35) is a phosphoprotein that is associated with the nucleocapid. It is a cofactor for viral RNA polymerase activity.
Virus protein (VP40) is associated with membranes. It directs budding of virus envelopes at the plasma membrane to form virions.
Glycoprotein (GP) is a heavily glycosylated type I transmembrane protein. It’s responsible for both receptor binding and fusion with cellular membranes. It is cleaved into two subunits: GP1, N-terminal portion and a GP2, C terminal portion. Each has a membrane anchor and fusion peptide.
Secreted glycoprotein (sGP) is a glycosylated protein that shares N-terminal amino acids with GP but it has a distinct C-terminus because of RNA editing and its different oligomeric structure. It lacks a membrane anchor and is secreted. It is not present in virions and has no known function.
Virus protein (VP30) is associated with the nucleocapsid. It activates transcription.
Virus protein (VP24) is associated with membranes but has no known function.
Large protein (L) is a viral RNA polymerase.
Nucleoprotein (NP) is a highly phosphorylated protein that forms the helical nucleocapid.
Virus protein (VP35) is a phosphoprotein that is associated with the nucleocapid. It is a cofactor for viral RNA polymerase activity.
Virus protein (VP40) is associated with membranes. It directs budding of virus envelopes at the plasma membrane to form virions.
Glycoprotein (GP) is a heavily glycosylated type I transmembrane protein. It’s responsible for both receptor binding and fusion with cellular membranes. It is cleaved into two subunits: GP1, N-terminal portion and a GP2, C terminal portion. Each has a membrane anchor and fusion peptide.
Secreted glycoprotein (sGP) is a glycosylated protein that shares N-terminal amino acids with GP but it has a distinct C-terminus because of RNA editing and its different oligomeric structure. It lacks a membrane anchor and is secreted. It is not present in virions and has no known function.
Virus protein (VP30) is associated with the nucleocapsid. It activates transcription.
Virus protein (VP24) is associated with membranes but has no known function.
Large protein (L) is a viral RNA polymerase.
Structure of Ebola (7)
Gene map (1)
Attachment, Transcription, Replication, and Release
Attachment:
Ebola’s only surface protein, GP, mediates the binding to cellular receptors. GP1 is involved in cellular attachment while GP2 is believed to mediate fusion.
Transcription:
Ebola replicates within the cytoplasm. Both mRNA synthesis and genome replication uses the negative-strand as a template. The 3’ end of the genome contains a promoter for the viral RNA polymerase and packaging signals for the assembly of the nucleocapsid. Genes are transcribed sequentially from the 3’ end of the genome to create 7 subgenomic mRNAs. mRNAs have a 5’ CAP and a 3’ poly(A) tail. The poly(A) tails are generated by stuttering of the viral RNA polymerase at a run of uridine residues next to each transcription termination signal sequence. Two GP proteins are synthesized by a unique process to Ebola, transcriptional editing. A secreted glycoprotein sGP, and an anchored GP. Both proteins share homology at their N-termni, but have different C-terminal sequences. The two proteins differ by an A residue. If mRNA is unedited sGP will be created, however if viral RNA polymerase pauses and “stutters” at a U stretch, it may add an adenosine residue into the mRNA. This pushes the reading frame downstream by one nucleotide to make the GP protein 676 amino acids long. Since the GP protein is produced by a stuttering mechanism, it occurs less frequently than the sGP protein. High levels of mRNA for the nucleocapsid protein are preferential transcribed due to the formation of secondary structures at the 3’ end, overlapping genes, gene order, and the presence of duplicated termination sites. Accumulation of NP shifts Ebola to begin replication.
Replication:
In order for the Ebola Virus to replicate, it must first synthesize a full-length complementary antigenome (RI-1), and this antigenome will act as a template for the synthesis of progeny negative-stranded RNA molecules. The RI-2 results in the full-length genome produced. The RNA genome is packed into nucleocapsids during replication, concerted assembly.
Release:
Viral particles bud through the plasma membrane where viral GP’s are inserted. VP40 is associated with the viral envelope. Directs budding for the virus and virion formation.
Ebola’s only surface protein, GP, mediates the binding to cellular receptors. GP1 is involved in cellular attachment while GP2 is believed to mediate fusion.
Transcription:
Ebola replicates within the cytoplasm. Both mRNA synthesis and genome replication uses the negative-strand as a template. The 3’ end of the genome contains a promoter for the viral RNA polymerase and packaging signals for the assembly of the nucleocapsid. Genes are transcribed sequentially from the 3’ end of the genome to create 7 subgenomic mRNAs. mRNAs have a 5’ CAP and a 3’ poly(A) tail. The poly(A) tails are generated by stuttering of the viral RNA polymerase at a run of uridine residues next to each transcription termination signal sequence. Two GP proteins are synthesized by a unique process to Ebola, transcriptional editing. A secreted glycoprotein sGP, and an anchored GP. Both proteins share homology at their N-termni, but have different C-terminal sequences. The two proteins differ by an A residue. If mRNA is unedited sGP will be created, however if viral RNA polymerase pauses and “stutters” at a U stretch, it may add an adenosine residue into the mRNA. This pushes the reading frame downstream by one nucleotide to make the GP protein 676 amino acids long. Since the GP protein is produced by a stuttering mechanism, it occurs less frequently than the sGP protein. High levels of mRNA for the nucleocapsid protein are preferential transcribed due to the formation of secondary structures at the 3’ end, overlapping genes, gene order, and the presence of duplicated termination sites. Accumulation of NP shifts Ebola to begin replication.
Replication:
In order for the Ebola Virus to replicate, it must first synthesize a full-length complementary antigenome (RI-1), and this antigenome will act as a template for the synthesis of progeny negative-stranded RNA molecules. The RI-2 results in the full-length genome produced. The RNA genome is packed into nucleocapsids during replication, concerted assembly.
Release:
Viral particles bud through the plasma membrane where viral GP’s are inserted. VP40 is associated with the viral envelope. Directs budding for the virus and virion formation.
Mechanism of virus replication, transcription, translation, assembly, and release (6)
Another image of virus building (7)
Sunday, October 14, 2007
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