Family: filoviridae
Viral hemorrhagic fevers
Introduction
Filoviridae means viral hemorrhagic fevers, a very high level of internal bleeding, family consists of two viruses: Marburg & Ebola viruses, Ebola has sub-types: Tai Forest, Sudan, Reston, Zaire & Bundibugyo, the virus concerned with the current outbreaks, is the Zaire species.
Mortality rate is high ranges between 30%sometimes 50% to 90%, depending on the virus, Ebola Reston is considered to be the one with low pathogenicity for humans
History
The virus first recorded in 1976 in ''Yambuku'' democratic republic of Congo it was then known as Zaire & Nzara, South Sudan, it first appeared in Ebola river for which the Ebola virus was named, It presents itself like the flu or malaria, symptoms resulted due to Ebola are severe headaches, diarrhea, vomiting, fever, muscle pain, weakness, stomach pain and bleeding among other things symptoms can appear from 2 to 21 days but the average time is between 8 to 10 days.
In December 2013 in west African countries of Guinea it was later confirmed in March 2014 then emerged to Liberia & Sierra Leone, they became the center of infection and some of these areas 90% of the patients died.
Then the disease prevailed to Europe and USA such as in Texas due to the travels between the cities, by far the cases has been growing more than 21,000 since January 2015.
Due to the several cases happened since 1976, we concluded that most of the countries and regions that have had this epidemic is usually countries of poor infrastructure, low economic level and very bad medical care.
Structure & Function
-Diameter: 80nm
-Length: 970nm
-Shape: filamentous, cylindrical or tubular-like, resembles a U-shape or takes the shape of number ''6'', pleomorphism '' as definition is the presence of more than one distinct shape'' (biological feature)
-Lipid( fatty) membrane, with glycoproteins on the surface of the virus as antigens for binding, glycoproteins are any class of proteins with carbohydrate group attached to the polypeptide chain then a viral capsid, ''capsid: a protein shell usually made to surround the viral genetic material'' in our case it is a negative-sense RNA strand '' negative-sense RNAs their genome has to be transcribed as soon as the virus enters the host cell in order to carry out replication''
Ebola virus has of approximately 19,000 base pairs, the 3' terminus is not polyadenylated & the virus encodes seven structural proteins: nucleoproteins (NP) '' are proteins structurally associated or presented with nucleic acids DNA and RNA such as histone proteins, VP35 (polymerase cofactor) in the transcription & replication complex in RNA polymerase also blocks phosphorylation and activation of interferon regulatory factor 3 (IRF3) '' IRF3 briefly is a critical transcriptional factor for the induction of interferons alpha & beta.
VP40 it is the primary viral matrix protein means it organizes, covers and maintains the the virion structure, attached directly to the cell's membrane and provides budding function, in some RNA viruses it acts as a bridge between the membrane and nucleocapsid
GP, glycoproteins we mentioned that before saying they are found on the surface of the Ebola virus, acting as antigens for binding sites. Recall GP as definition? '' proteins attached with it any class of carbohydrate functional groups''
VP30 ''transcription activator'' phosphoprotein (any protein other than nucleic acid & phospholipid attached with it phosphorous) essential for the initiation of the Ebola virus transcription also an RNA binding protein.
In December 2013 in west African countries of Guinea it was later confirmed in March 2014 then emerged to Liberia & Sierra Leone, they became the center of infection and some of these areas 90% of the patients died.
Then the disease prevailed to Europe and USA such as in Texas due to the travels between the cities, by far the cases has been growing more than 21,000 since January 2015.
Due to the several cases happened since 1976, we concluded that most of the countries and regions that have had this epidemic is usually countries of poor infrastructure, low economic level and very bad medical care.
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| Mortality rates of Ebola virus |
Structure & Function
-Diameter: 80nm
-Length: 970nm
-Shape: filamentous, cylindrical or tubular-like, resembles a U-shape or takes the shape of number ''6'', pleomorphism '' as definition is the presence of more than one distinct shape'' (biological feature)
-Lipid( fatty) membrane, with glycoproteins on the surface of the virus as antigens for binding, glycoproteins are any class of proteins with carbohydrate group attached to the polypeptide chain then a viral capsid, ''capsid: a protein shell usually made to surround the viral genetic material'' in our case it is a negative-sense RNA strand '' negative-sense RNAs their genome has to be transcribed as soon as the virus enters the host cell in order to carry out replication''
Ebola virus has of approximately 19,000 base pairs, the 3' terminus is not polyadenylated & the virus encodes seven structural proteins: nucleoproteins (NP) '' are proteins structurally associated or presented with nucleic acids DNA and RNA such as histone proteins, VP35 (polymerase cofactor) in the transcription & replication complex in RNA polymerase also blocks phosphorylation and activation of interferon regulatory factor 3 (IRF3) '' IRF3 briefly is a critical transcriptional factor for the induction of interferons alpha & beta.
VP40 it is the primary viral matrix protein means it organizes, covers and maintains the the virion structure, attached directly to the cell's membrane and provides budding function, in some RNA viruses it acts as a bridge between the membrane and nucleocapsid
GP, glycoproteins we mentioned that before saying they are found on the surface of the Ebola virus, acting as antigens for binding sites. Recall GP as definition? '' proteins attached with it any class of carbohydrate functional groups''
VP30 ''transcription activator'' phosphoprotein (any protein other than nucleic acid & phospholipid attached with it phosphorous) essential for the initiation of the Ebola virus transcription also an RNA binding protein.
VP24 is the secondary viral matrix protein attached beside VP40 '' the primary viral matrix protein'' minor component of the virion, it has a role in the formation of nucleocapsid & effect on transcription and replication of the viral genome, Last but not least, RNA polymerase (l).
According to the world health organization (WHO), humans aren't infectious until they develop symptoms so whenever you find yourself or someone else developing symptoms of Ebola virus, seek medical care as soon as possible and avoid contact with anyone.
The symptoms developed by a person contract with Ebola are the following:
As we notice, it is very severe, the fatal range of such disease is between 50% - 90%, seeking medical care immediately, obeying the precautions and the good medical care & the will of surviving and the status of the patient's immune response can develop a good recovery from Ebola, developing the suitable antibodies against such disease will help you get over it also such antibodies are said to be at least surviving in your body for 10 years or so.
Two crucial things we are going to talk about next, first the mechanism of prevalence in our body & the steps of replication of Ebola virus.
The guard cells such as macrophages and monocytes which are infected are ordered to send messenger chemical proteins ''cytokines'' to the blood vessels to releases its fluids inside our body causing internal bleeding, another areas such as liver, spleen and kidneys which are kind of the organs that maintains and balance our bodily fluids also gets infected by the Ebola virus leading to organ failure but in this case we can call it a massive or huge multiple organs failure besides the lungs which also gets shutdown due to the unstoppable attack of the virus on our immune system, the immune cells launches a cytokine storm at which each immune cell releases a massive secretion of chemical messengers called ''cytokines'' that at such case it affects our organ tissues and blood vessels,Paradoxically, the healthier the immune system, the more damage it can do to itself, so the copious amount of fluids spread all over the body leads to what this family is described by ''hemorrhagic fevers'' the body becomes seriously dehydrated and at this time, the chance of dying is very high.
Luckily, Ebola virus isn't high contagious, the only ways you can contract Ebola is to come in contact with bodily fluids of an infected person such as urine, semen, saliva, mucous, blood, feces or vomit and from fruit bats said to be '' natural reservoirs'' of Ebola virus so a conclusion is that Ebola virus is a type of zoonotic disease '' diseases that can be spread between animals and humans'' such as Dengue, yellow fever, HIV, malaria, Marburg, rabies, swine flu and much more, so other animals can be infected with Ebola since animals feed on each other and one day or another it will come to a fruit bat eaten by any other wild-type animals which people usually hunt down and uses its meat ''bush meat'' and that is one of the reasons why some people contracted Ebola in USA.
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| Ebola virus anatomy |
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| C.section of close view of Ebola virus |
Signs & symptoms of the Ebola virus disease
Symptoms and signs of Ebola virus disease shows up from 2 to 21 days after the exposure to Ebola virus but the average ranges from 8 to 10 days, Ebola virus can kill its own patient within 7 to 14 days after developing symptoms, a person contracted with Ebola virus can be found hidden in his semen up to 7 weeks.According to the world health organization (WHO), humans aren't infectious until they develop symptoms so whenever you find yourself or someone else developing symptoms of Ebola virus, seek medical care as soon as possible and avoid contact with anyone.
The symptoms developed by a person contract with Ebola are the following:
- Headache
- Aches in muscles & joints
- Hiccups
- Abdominal pains
- High fever, usually more than 38.5 C*
- Sore throat
- Weakness
- Swelling
- Diarrhea
- Stomach pains
- Internal & external hemorrhage (bleeding)
- Fatigue
- Chilling
- Vomiting
- Nausea
- Red eyes & bleeding coming out of the eyes
- Chest pain and cough
- Rash
- Kidney and liver failures
- Severe weight loss
As we notice, it is very severe, the fatal range of such disease is between 50% - 90%, seeking medical care immediately, obeying the precautions and the good medical care & the will of surviving and the status of the patient's immune response can develop a good recovery from Ebola, developing the suitable antibodies against such disease will help you get over it also such antibodies are said to be at least surviving in your body for 10 years or so.
Two crucial things we are going to talk about next, first the mechanism of prevalence in our body & the steps of replication of Ebola virus.
First: Mechanism of prevalence in our body
Ebola virus directly attacks our immune system, it mainly goes onto one of your important immune antigen presenting cells ''Dendritic cells'' or Langerhan cells & macrophages (guard cells) both are type of your innate immune system cells, these cells have type two major histocompatibility complexes, once it penetrate through the dendritic cell releasing its components inside it starts taking control of it and uses its machinery to build more of itself once not only it infects the dendritic cells but it also trick the anti-viral cells and some specialized cells by sending them messenger proteins that end these cells life prematurely( meaning when they are still in their inactive states), there are cells such as Natural killer cells are present just to hunt down any virus-infected cells by sending enzymes ''granzymes'' which causes holes named ''perforins'' in the infected cell membrane in what we call ''Apoptosis'' (=program cell death).Unfortunately, these cells also gets infected by Ebola virus.The guard cells such as macrophages and monocytes which are infected are ordered to send messenger chemical proteins ''cytokines'' to the blood vessels to releases its fluids inside our body causing internal bleeding, another areas such as liver, spleen and kidneys which are kind of the organs that maintains and balance our bodily fluids also gets infected by the Ebola virus leading to organ failure but in this case we can call it a massive or huge multiple organs failure besides the lungs which also gets shutdown due to the unstoppable attack of the virus on our immune system, the immune cells launches a cytokine storm at which each immune cell releases a massive secretion of chemical messengers called ''cytokines'' that at such case it affects our organ tissues and blood vessels,Paradoxically, the healthier the immune system, the more damage it can do to itself, so the copious amount of fluids spread all over the body leads to what this family is described by ''hemorrhagic fevers'' the body becomes seriously dehydrated and at this time, the chance of dying is very high.
Luckily, Ebola virus isn't high contagious, the only ways you can contract Ebola is to come in contact with bodily fluids of an infected person such as urine, semen, saliva, mucous, blood, feces or vomit and from fruit bats said to be '' natural reservoirs'' of Ebola virus so a conclusion is that Ebola virus is a type of zoonotic disease '' diseases that can be spread between animals and humans'' such as Dengue, yellow fever, HIV, malaria, Marburg, rabies, swine flu and much more, so other animals can be infected with Ebola since animals feed on each other and one day or another it will come to a fruit bat eaten by any other wild-type animals which people usually hunt down and uses its meat ''bush meat'' and that is one of the reasons why some people contracted Ebola in USA.
Replication of Ebola virus
As we know Ebola virus infects firstly your guard cells & antigen-presenting cells of your body macrophages and dendritic cells, these immune cells surface antigens has something called DC-SIGN (dendritic cells special intracellular ''means inside the cell'' adhesion molecule 3-grabbing non-integrin) also known as CD209 encoded by CD209 gene,adding that it is a C-type lectin receptor (lectins are type of proteins that can bind to the cell membranes, they recognize and bind specific carbohydrates found on the surfaces of cells also plays a role in interaction and communication between cells for recognition) , Glycoproteins surface antigens and receptors of the Ebola virus attaches to the target cell's receptors and eventually binds to it.
The virus then starts penetrating the cell's surface ( endocytosed) later enters an early endosome ''endosomes are membrane-bounded vesicles'' by macropinocytosis also known as clathrin-mediated endocytoses ( cytosis means cell action, pinocytosis is an action the cells do to take up some nutrients by making a folds of its own membrane surrounding the nutrients or whatever molecules it is taking in a vesicle and receptors for binding)Ultimately, the virus glycoproteins receptors binds to the cell's receptors inwardly making an invagination taking the virus inside.
(Clathrin is a protein found on the surface of these cells that has a role in the formation of these vesicles)
Also NP-C1 Niemann-Pick C1 is a hydrophobic (hates water) lysosomal integral membrane that plays an essential role in cholesterol regulation, transport and storage facilitates the entrance of Ebola virus into your cell endosomes and lysosomes, without it the virus cannot leave the vesicles in order to start the infection.
The virus then starts penetrating the cell's surface ( endocytosed) later enters an early endosome ''endosomes are membrane-bounded vesicles'' by macropinocytosis also known as clathrin-mediated endocytoses ( cytosis means cell action, pinocytosis is an action the cells do to take up some nutrients by making a folds of its own membrane surrounding the nutrients or whatever molecules it is taking in a vesicle and receptors for binding)Ultimately, the virus glycoproteins receptors binds to the cell's receptors inwardly making an invagination taking the virus inside.
(Clathrin is a protein found on the surface of these cells that has a role in the formation of these vesicles)
Also NP-C1 Niemann-Pick C1 is a hydrophobic (hates water) lysosomal integral membrane that plays an essential role in cholesterol regulation, transport and storage facilitates the entrance of Ebola virus into your cell endosomes and lysosomes, without it the virus cannot leave the vesicles in order to start the infection.
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| http://www.microbiologyinfo.com/tag/ebola/ |
The fusion happens when the pH ( concentration of hydrogen ion in any solution) is low or with NPC1 binding.
Once the virus penetrate through the endosomes, it dissolves its outer hull, leaves its genetic material, nucleoproteins and enzymes, transcription phase starts now, RNA polymerase found on the RNA strand of the virus transcribes the RNA strand into seven monocistronic mRNAs ( monocistronic mRNA means an mRNA that codes only for one protein) the cell's machinery now is taken control via the virus which makes it produce the required nucleoproteins, tRNA molecules, etc..
The polymerase slides over the RNA strand 3' to 5' order transcribing the genes into particular proteins.
After translation, replication phase starts at which the negative-sense ssRNA strand acts as template to synthesize a complementary +ssRNA which is then used to synthesize a -ssRNA which is encapsidated with its proteins forming a new virus.
Now the virus is capsidated having its genetic material, nucleoproteins and enzymes inside, it is about time it leaves the cell to continue infecting other cells. Budding phase initiates.
The virus uses the cellular ESCRT (endosomal sorting complex required for ''transport'' ) system '' it is machinery used to control the key cellular processes, the ESCRT proteins functions by binding membrane, generating curvatures and presence of some enzymes to complete the process'' ESCRT has various functions such as its enrollment in cytokineses, the ESCRT family consists of ESCRT -0, ESCRT- 1, ESCRT-ll & ESCRT-lll
ESCRT-0, ESCRT-l & ESCRT-ll functions in deformation of membranes & primarily involved in cargo sorting while ESCRT-lll cleaves (breaks down) the buds' neck from its cytosolic face.Last but not least, the VPS4 disassembles the complex and the virion is free from the cell now.
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| http://www.microbiologyinfo.com/tag/ebola/ |
(Cytosolic face is the surface of a bio-membrane ''structure bounding a cell membrane or cell organelle it contains lipids, proteins, glycolipids, steroids and much more'' directed towards the cytoplasm)
Intravenous fluids regulation is carefully made to achieve and maintain an isotonic environment in the body ( used for cases of dehydration) usually when a person's body is dehydrated, fluid containing water and dissolved salts known as electrolytes such as Na & K, there are two types in which intravenous fluids are used: 1) Acute fluid resuscitation 2) Maintenance fluids
-Acute fluid resuscitation, which is important for our case, is used in the cases of hypovolaemia (hypo=low - vol=volume - aemia=anemia or loss) a loss in blood volume e.g. hemorrhage, severe diarrhea & vomiting, burns and much more symptoms like those mentioned in our case (Ebola)
There are three main types of fluids crystalloids which contains small molecules that can easily pass through the membranes of the cell e.g. Normal saline 0.9% sodium chloride, Hartmann's solution and 5% glucose or dextrose.
Just a very small example of what some of these crystalloids contain, normal saline 0.9% sodium chloride has sodium 154mmol/L & chloride 154mmol/L.
Other treatments that help you get over Ebola virus which has saved many doctors who unfortunately contracted the Ebola virus from their patients, is a serum made from the blood plasma of other patients or doctors who had contracted and survived from the virus and, then injected into their bodies, which with the proper care later helped them get over the virus and develop an immune response but such thing is considered to be a type of passive humoral immunity since remember? the blood plasma contains immunoglobulins ( antibodies) produced by those whom survived the ebolavirus but still yet researches are ongoing for such type of antibodies and a way to develop a vaccine through this.
Throughout the medicine and this incredible field of science, not only medicine-ways are the ones needed to help one survive any disease but also resistance to fatal disease like this requires the will and your believe in yourself that you can do, thrive and get over such disease beside taking, seeking and obeying medical care sharply will definitely let you defeat such disgusting fatal viruses.
(read this story about one of Ebola virus survivors and how it is inspiring, Dr. Melvin Korkor: http://archive.eboladeeply.org/articles/2014/09/6124/survivor-story-dr-melvin-korkor/)
The following link provides various medical equipment used for Ebola care according to WHO: http://www.who.int/medical_devices/meddev_list_ebola_25nov_en.pdf?ua=1
Last but not least, no matter what happen, the humans has always had and still has an infinite potential of evolution which will succeed in eliminating such disease and consign it in its rightful place..... the history books.
3)Introduction to IV fluids (very informative)
4)Mechanism of spreading ( in a nutshell )
5)What we know and don't know about Ebola
6) Another video to help you mechanism of infection
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| Ebola virus replication |
Are there any cures found for Ebola virus disease?Vaccines?
Currently no, by far no cures discovered but there are few ways that contribute in controlling and decreasing the infection rate of the Ebola virus in our body such as Intravenous fluids (IV), balancing electrolytes ( body salts), maintaining oxygen status and blood pressure until the body generates a powerful immune response,Intravenous fluids regulation is carefully made to achieve and maintain an isotonic environment in the body ( used for cases of dehydration) usually when a person's body is dehydrated, fluid containing water and dissolved salts known as electrolytes such as Na & K, there are two types in which intravenous fluids are used: 1) Acute fluid resuscitation 2) Maintenance fluids
-Acute fluid resuscitation, which is important for our case, is used in the cases of hypovolaemia (hypo=low - vol=volume - aemia=anemia or loss) a loss in blood volume e.g. hemorrhage, severe diarrhea & vomiting, burns and much more symptoms like those mentioned in our case (Ebola)
There are three main types of fluids crystalloids which contains small molecules that can easily pass through the membranes of the cell e.g. Normal saline 0.9% sodium chloride, Hartmann's solution and 5% glucose or dextrose.
 |
| Hartmann's solution IV |
Just a very small example of what some of these crystalloids contain, normal saline 0.9% sodium chloride has sodium 154mmol/L & chloride 154mmol/L.
Other treatments that help you get over Ebola virus which has saved many doctors who unfortunately contracted the Ebola virus from their patients, is a serum made from the blood plasma of other patients or doctors who had contracted and survived from the virus and, then injected into their bodies, which with the proper care later helped them get over the virus and develop an immune response but such thing is considered to be a type of passive humoral immunity since remember? the blood plasma contains immunoglobulins ( antibodies) produced by those whom survived the ebolavirus but still yet researches are ongoing for such type of antibodies and a way to develop a vaccine through this.
Throughout the medicine and this incredible field of science, not only medicine-ways are the ones needed to help one survive any disease but also resistance to fatal disease like this requires the will and your believe in yourself that you can do, thrive and get over such disease beside taking, seeking and obeying medical care sharply will definitely let you defeat such disgusting fatal viruses.
(read this story about one of Ebola virus survivors and how it is inspiring, Dr. Melvin Korkor: http://archive.eboladeeply.org/articles/2014/09/6124/survivor-story-dr-melvin-korkor/)
The following link provides various medical equipment used for Ebola care according to WHO: http://www.who.int/medical_devices/meddev_list_ebola_25nov_en.pdf?ua=1
Last but not least, no matter what happen, the humans has always had and still has an infinite potential of evolution which will succeed in eliminating such disease and consign it in its rightful place..... the history books.
References used:
- http://groups.molbiosci.northwestern.edu/holmgren/Glossary/Definitions/Def-M/monocistronic_mRNA.html
- http://archive.eboladeeply.org/background/basics/ <-there you can find various journals about ebola
- https://deepblue.lib.umich.edu/handle/2027.42/110318
- http://www.who.int/mediacentre/factsheets/fs103/en/
- http://www.ncbi.nlm.nih.gov/pubmed/10721995
- http://www.microbiologyinfo.com/tag/ebola/ (special thanks)
- https://micro.magnet.fsu.edu/cells/endosomes/endosomes.html
- http://ed.ted.com/lessons/what-we-know-and-don-t-know-about-ebola-alex-gendler
- https://www.youtube.com/channel/UCH4BNI0-FOK2dMXoFtViWHw
- https://www.youtube.com/channel/UCsXVk37bltHxD1rDPwtNM8Q
- https://www.youtube.com/channel/UCPY9IKSkr2GfFW5jbgA5Qbw
- http://geekymedics.com/
- http://www.washingtonpost.com/wp-srv/special/health/how-ebola-spreads/#b10g15t20w14 <-- check out this simulation showing how deadly Ebola virus is comparing to other viruses
- http://www.uniprot.org/uniprot/Q05127
- https://collab.itc.virginia.edu/access/content/group/f85bed6c-45d2-4b18-b868-6a2353586804/P/Ch24_Coleman_G_Niemann-Pick_C1/Coleman-NiemannPickC1_NPC1.html
- http://www.ncbi.nlm.nih.gov/pubmed/12223058
Videos
1)Discusses the mechanism of infection
2)Facts about Ebola virus3)Introduction to IV fluids (very informative)
4)Mechanism of spreading ( in a nutshell )
5)What we know and don't know about Ebola
6) Another video to help you mechanism of infection
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