- Ebola virus causes a severe hemorrhagic fever in humans and non-human primates. It belongs to the filovirus family. - The natural reservoir of the virus is unknown, though fruit bats are suspected. It is transmitted via contact with bodily fluids. - The virus enters host cells and hijacks their machinery to replicate. It disrupts the host immune response, causing systemic damage and bleeding. No approved treatments exist, though supportive care is given. Isolation and protective equipment are emphasized for control.

1. EBOLA VIRUS
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2. BACKGROUND:-
Ebola viruses (EBOVs) belong to the Filoviridae family and arecharacterized by a
negative stranded RNA structure .
It should benoted that the nomenclature and disease classification of
thefiloviruseshas been a subject of intense discussion as summarized elsewhere .
Of the various filoviruses, EBOV has garnered worldwide attention dueto the
rapidity of acute hemorrhagic disease and the highly infectiousnature of the virus.
Discovered during the first documented outbreak ofEBOV disease in the town of
Yambuku in the Democratic Republic ofCongo (DRC) in 1976, these viruses have
caused outbreaks of variablemagnitude in several west and equatorial African
countries.
In the mostrecent outbreak in West Africa between 2013 and 2016, about
28,000cases were confirmed and up to 11,000 deaths were reported,
thusdemonstrating the high mortality of this condition.

3. The most recent EVD outbreak has been ongoing in the Democratic Republic of Congo
(Equateur Province) since June 2020. As of 9 August 2020, there had been 79 confirmed and
probable cases.
There are 6 species of Ebola virus, 4 of which have caused disease in humans:
•Zaïre ebolavirus (EBOV)
•Sudan ebolavirus (SUDV)
•Tai Forest (TAFV) (formerly known as Ebola Ivory Coast)
•Bundibugyo ebolavirus (BDBV)
Natural reservoir
Ebola is believed to be zoonotic, however, the natural reservoir is unknown, despite extensive
investigations. Non-human primates have been a source of human infection, however, they are not
thought to be the reservoir as they develop severe, fatal illness when infected.
High numbers of animal carcasses were noted in surrounding areas prior to outbreaks in Gabon
and DRC, and recovered carcasses were infected with a variety of strains of Ebola virus suggesting they
were not the reservoir but had been infected by more than one source.
Harvesting of migrating fruit bats was thought to be the source of a large outbreak in the DRC in 2007.

5. Structure of Ebola Virus
It falls under the Filoviridae family.
The virion is filamentous, enveloped measuring 800 nm length and 80 nm in
diameter.
It comprises of negative sense, single stranded RNA genome.
Structural proteins associated with the nucleocapsid are the nucleoprotein
(NP), VP30, VP35, and the polymerase (L) protein.
Membrane-associated proteins are the matrix protein (VP40), VP24, and the
GP (peplomer glycoprotein).
The nucleocapsid is encapsulated by an outer viral envelope originating from
the host cell membrane with characteristic 10 nm long viral glycoprotein (GP)
spikes that initiates attachment.

7. Genome of Ebola Virus
It comprises of linear, negative-stranded RNA genome, about 18-19 kb in size.
The genome encodes for seven proteins which includesGP- transmembrane
glycoprotein that helps in attachment
NP- nucleoprotein necessary for capsid assembly and packaging
VP24- antiviral inhibitor, suppresses interferon production in the host cell
VP35- inhibits interferon production or antiviral response to ds RNA.
VP30- transcription anti-terminator
VP40- maintaining the structural integrity of the virion, necessary for capsid assembly
and budding
L protein- viral polymerase

10. TRANSMISSION:-
It spreads to people by contact with the skinor bodily
fluids of an infected animal, like a monkey, chimp, or fruit
bat.
Human to human transmission via direct contact with
blood and secretions, by contact with blood and
secretions that remain on clothing, and by needles and/or
syringes or other medical supplies used to treat Ebola-
infected patients.

12. Replication of Ebola Virus
Entry is mediated by attachment of virus to host receptorslike DC-SIGN and DC-
SIGNR through GP glycoprotein.
The virion enters the cell by Macropinocytosis or Clathrin-mediated endocytosis.
GP1 interacts with host NPC1, in late macropinosome and promotes fusionof
virus membrane with the vesicle membrane.
The ribonucleocapsid is then released into the cytoplasm.
Sequential transcription, viral mRNAs are capped and polyadenylated
by polymerase stutteringin the cytoplasm.
VP30 is an important transcription activation factor for viral genome
transcription, while VP24 is an inhibitor to this process.

13. Replication presumably starts by binding of RNA dependent RNA polymerase
complex to the leader sequence on the encapsidated (-)RNA genome.
The antigenome is concomitantly encapsidated during replication.
The ribonucleocapsid interacts with the matrix protein VP40, and buds via the
host ESCRT (endosomal sorting complex required for transport) complexes from
the plasma membrane, releasing the virion.

15. Pathogenesis of Ebola Virus

16. The Ebola virusenters the host through basic entry paths. It can enter through mucous
membranes, broken skin, or by parental transmission. It is capable of binding to these
membranes of essentially every human cell.
The entry of the cell is controlled by a glycoprotein that is responsible for binding the
virus to the cell receptors.
The specific cytokines the virus provokes are the proteins that prompt the natural
inflammatory response.
The inflammatory response induced by the infection of the virus is so drastic that it
begins to cause damage to the host cells.
By deregulating the cytokines, the virus is able to spread rapidly throughout the host.
Ebola virus capability to inhibit the synthesis of proteins that activate the response when
the cell has been infected.
A protein produced by the Ebola virus, VP35 is capable of inhibiting the synthesis of a
specific INFs protein.

17. Another way that the virus disrupts the INF response is through the production of
protein VP24.
A third way the virus is capable of defending itself from the antiviral response of the
human body is through the glycoprotein inhibition of tetherin expression.
When the virus spreads throughout the body, one of its targets are hepatic cells, or
liver cells.
The Ebolavirusis capable of inducing necrosis of the hepatic cells, which can result in
multiple outcomes.
When the virus is killing the hepatic cells, the liver can’t synthesize enough coagulant
proteins, allowing the hemorrhaging to happen.
The necrosis doesn’t only shut down the hemorrhaging proteins but also shuts down
the liver functions, rendering the liver useless to the infected human.
Other organs that undergo a similar attack from the virus are the spleen, thymus, and
lymph nodes.
Similar to the liver, these organs see lymphatic depletion and necrosis due to the
infection.
The overall pathogenesis and pathology by Ebola virus include:
1. Cell entry and tissue damage
2. Gastrointestinal dysfunction
3. Systemic inflammatory response
4. Coagulation defects
5. Impairment of adaptive immunity

18. Clinical manifestations of Ebola Virus
In early stages patients feel like the fluor other illnesses.
The incubation period is 2 to 21 days and symptoms usually include:
High fever
Headache
Joint and muscle aches
Sore throat
Weakness
Stomach pain
Lack of appetite
Progression of Ebola symptoms includes diarrhea, vomiting, stomach pain, hiccups, rash, and
internal and external bleeding in many patients.
Laboratory finding include low white blood count, low platelet count and elevated liver
enzymes.
Other complications includes sever bleeding, failure of multiple organs, shock.

20. Lab Diagnosis of Ebola Virus
Specimen: Blood or body fluids, semen, Oral swabs,
1. Antibodies appear later in disease course or after recovery (IgM
and IgG) that are detected by ELISA.
2. Viral antigens in serum can be detected by ELISA, providing a
rapid screening test of human samples.
3. RT-PCR is also used on clinical specimens.
4. Virus isolates can be cultured in cell lines such as Vero and MA-
104 monkey cell lines.

21. Treatment of Ebola Virus
No proven treatment in use and no approved vaccine.
Secondary treatment during disease progression include:
Providing intravenous fluids (IV) and balancing electrolytes (body
salts).
Maintaining oxygen status and blood pressure.
Treating other infections if they occur.

22. Prevention and control of Ebola Virus
Avoidance of funeral or burial rituals that require handling the body of person
who has died from Ebola.
Avoidance of contact with bats and non human primates or blood, fluids, and
raw meat prepared from these animals.
Healthcare workers who may be exposed to people with Ebola should wear
appropriate personal protective equipment (PPE) and practice proper infection
control and sterilization measures.
Early testing and isolation of the patient plus barrier protection for caregivers
(mask, gown, goggles, and gloves) is very important to prevent other people from
getting infected.

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