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EBOLA VIRUS
Ebola virus (EBOV) causes an extremely severedisease inhumans and in nonhumanprimates in
the form ofviral hemorrhagic fever.EBOV is aselect agent,World Health Organization Risk
Group 4 Pathogen (requiringBiosafety Level 4-equivalent containment),National Institutes of
Health/National Institute of Allergy and Infectious Diseases Category A PriorityPathogen,Centers for Disease Control and PreventionCategory A Bioterrorism Agent,and listed
as a Biological Agent for Export Control by theAustralia Group.
Ebola virus (abbreviated EBOV) was first described in 1976 by David Finkes.[1][2][3]
Today, the
virus is the single member of thespeciesZaire ebolavirus,which is included into
thegenusEbolavirus,familyFiloviridae,orderMononegavirales.The name Ebola virus is
derived from theEbola River (a river that was at first thought to be in close proximity to the area
inZaire where the first recorded Ebola virus disease outbreak occurred) and
thetaxonomicsuffix virus.[4]
According to the rules for taxon naming established by theInternational Committee onTaxonomy of Viruses (ICTV), the name Ebola virus is always to becapitalized,but is
neveritalicized,and may beabbreviated (with EBOV being the official abbreviation).
Previous designations
Ebola virus was first introduced as a possible new "strain" ofMarburg virus in 1977 by two
different research teams.[1][2]
At the same time, a third team introduced the name Ebola
virus.[3]
In 2000, the virus name was changed to Zaire Ebola virus,[5][6]
and in 2005 to Zaire
ebolavirus.[7][8]
However, most scientific articles continued to refer to Ebola virus or used the
terms Ebola virus and Zaire ebolavirus in parallel. Consequently, in 2010, the name Ebola viruswas reinstated.
[4]Previous abbreviations for the virus were EBOV-Z (for Ebola virus Zaire) and
most recently ZEBOV (for Zaire Ebola virus or Zaire ebolavirus). In 2010, EBOV was reinstated
as the abbreviation for the virus
A virus of the speciesZaire ebolavirusis an Ebola virus if it has the properties ofZaire
ebolaviruses and if itsgenome diverges from that of the prototype Zaire ebolavirus, Ebola virus
variant Mayinga (EBOV/May), by 10% at thenucleotide level
EBOV is one of four ebolaviruses that causesEbola virus disease (EVD) in humans (in the
literature also often referred to as Ebola hemorrhagic fever, EHF). In the past, EBOV has caused
the following EVD outbreaks:
Ebola virus disease (EVD) outbreaks due to Ebola virus (EBOV) infection
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bola_Riverhttp://en.wikipedia.org/wiki/Mononegaviraleshttp://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruseshttp://en.wikipedia.org/wiki/Filoviridaehttp://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruseshttp://en.wikipedia.org/wiki/Ebolavirushttp://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruseshttp://en.wikipedia.org/wiki/Zaire_ebolavirushttp://en.wikipedia.org/wiki/International_Committee_on_Taxonomy_of_Viruseshttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-Johnson1977-3http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Pattyn1977-1http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Pattyn1977-1http://en.wikipedia.org/wiki/Australia_Grouphttp://en.wikipedia.org/wiki/Bioterrorismhttp://en.wikipedia.org/wiki/Centers_for_Disease_Control_and_Preventionhttp://en.wikipedia.org/wiki/National_Institute_of_Allergy_and_Infectious_Diseaseshttp://en.wikipedia.org/wiki/National_Institutes_of_Healthhttp://en.wikipedia.org/wiki/National_Institutes_of_Healthhttp://en.wikipedia.org/wiki/Biosafety_level#Biosafety_level.C2.A04http://en.wikipedia.org/wiki/World_Health_Organizationhttp://en.wikipedia.org/wiki/Select_agenthttp://en.wikipedia.org/wiki/Viral_hemorrhagic_feverhttp://en.wikipedia.org/wiki/Primateshttp://en.wikipedia.org/wiki/Humanhttp://en.wikipedia.org/wiki/Ebola_virus_disease8/14/2019 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Year Geographic locationHuman cases/deaths
(case-fatality rate)
1976 Yambuku,Zaire 318/280 (88%)
1977 Bonduni,Zaire 1/1 (100%)
1988 Porton Down,United Kingdom 1/0 (0%) [laboratory
accident]
19941995- Woleu-Ntem andOgoou-Ivindo Provinces,Gabon 52/32 (62%)
1995 Kikwit,Zaire 317/245 (77%)
1996 Mayibout 2,Gabon 31/21 (68%)
1996 Sergiyev Posad,Russia 1/1 (100%) [laboratory
accident]
1996
1997
Ogoou-Ivindo Province,Gabon;Cuvette-Ouest
Department,Republic of the Congo
62/46 (74%)
2001
2002
Ogoou-Ivindo Province,Gabon;Cuvette-Ouest
Department,Republic of the Congo
124/97 (78%)
2002 Ogoou-Ivindo Province,Gabon;Cuvette-Ouest
Department,Republic of the Congo
11/10 (91%)
2002
2003
Cuvette-Ouest Department,Republic of the
Congo;Ogoou-Ivindo Province,Gabon
143/128 (90%)
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Ebola virus disease (EVD) outbreaks due to Ebola virus (EBOV) infection
Year Geographic locationHuman cases/deaths
(case-fatality rate)
2003
2004
Cuvette-Ouest Department,Republic of the Congo 35/29 (83%)
2004 Koltsovo,Russia 1/1 (100%) [laboratory
accident]
2005 Cuvette-Ouest Department,Republic of the Congo 11/9 (82%)
2007 Kasai Occidental Province,Democratic Republic of the
Congo
264/186 (71%)
2008
2009
Kasai Occidental Province,Democratic Republic of the
Congo
32/15 (47%)
2012 Kibaale District,WesternUganda 24/17 (71%)
2012 Isoro, Viadana, Dungu districts of Orientale
ProvinceDemocratic Republic of the Congo
62/34 (54%)
Structure
Electron micrographs of EBOV show them to have the characteristic threadlike structure of afilovirus.[9]
EBOV VP30 is around 288 amino acids long.[10]
The virions are tubular in general
form but variable in overall shape and may appear as the classic shepherd's crook or eyebolt, as
a Uor a 6, or coiled, circular, or branched; laboratory techniques, such ascentrifugation,may be
the origin of some of these formations.[11]
Virions are generally 80nm in diameter with a lipid
bilayer anchoring the glycoprotein which projects 7 to 10 nm long spikes from its
surface.[12]
They are of variable length, typically around 800 nm, but may be up to 1000 nm long.
In the center of the virion is a structure called nucleocapsid, which is formed by the helically
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wound viral genomic RNA complexed with the proteins NP, VP35, VP30, and L.[13]
It has a
diameter of 80 nm and contains a central channel of 2030 nm in diameter. Virally
encodedglycoprotein (GP) spikes 10 nm long and 10 nm apart are present on the outerviral
envelope of the virion, which is derived from the host cell membrane. Between envelope and
nucleocapsid, in the so-called matrix space, the viral proteins VP40 and VP24 are located .[14]
Genome
Each virion contains one molecule of linear, single-stranded,negative-sense RNA, 18,959 to
18,961 nucleotides in length. The 3 terminus is not polyadenylated and the 5 end is not capped.
It was found that 472 nucleotides from the 3' end and 731 nucleotides from the 5' end are
sufficient for replication.[15]
It codes for seven structural proteins and one non-structural protein.
The gene order is 3 leaderNPVP35VP40GP/sGPVP30VP24Ltrailer5;
with the leader and trailer being non-transcribed regions, which carry important signals to control
transcription, replication, and packaging of the viral genomes into new virions. The genomic
material by itself is not infectious, because viral proteins, among them the RNA-dependent RNA
polymerase, are necessary to transcribe the viral genome into mRNAs because it is a negative
sense RNA virus, as well as for replication of the viral genome. Sections of the NP and the Lgenes from filoviruses have been identified as endogenous in the genomes of several groups of
small mammals.[16]
Entry
NiemannPick C1 (NPC1)appears to be essential for Ebola infection. Two independent studies
reported in the same issue ofNature (journal) showed that Ebola virus cell entry and replication
requires the cholesterol transporter protein NPC1.[17][18]
When cells fromNiemann Pick Type C1
patients were exposed to Ebola virus in the laboratory, the cells survived and appeared immune
to thevirus,further indicating that Ebola relies on NPC1 to enter cells. This might imply that
genetic mutations in the NPC1 gene in humans could make some people resistant to one of the
deadliest known viruses affecting humans. The same studies described similar results withEbola's cousin in thefilovirus group,Marburg virus,showing that it too needs NPC1 to enter
cells.[17][18]
Furthermore, NPC1 was shown to be critical tofilovirus entry because it mediates
infection by binding directly to theviral envelope glycoprotein.[18]
A later study confirmed the
findings that NPC1 is a criticalfilovirus receptor that mediates infection by binding directly to
theviral envelopeglycoprotein and that the second lysosomal domain of NPC1 mediates this
binding.[19]
In one of the original studies, asmall molecule was shown to inhibit Ebola virus infection by
preventing the virus glycoprotein from binding to NPC1.[18][20]
In the other study, mice that were
heterozygous for NPC1 were shown to be protected from lethal challenge with mouse adapted
Ebola virus.[17]
Together, these studies suggest NPC1 may be potential therapeutic target for anEbola anti-viral drug.
Replication
Being acellular, viruses do not grow through cell division; instead, they use the machinery and
metabolism of a host cell to produce multiple copies of themselves, and they assemble in the
cell.[13]
http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Glycoproteinhttp://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid8219816-14http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid8219816-14http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid8219816-14http://en.wikipedia.org/wiki/Sense_(molecular_biology)http://en.wikipedia.org/wiki/Ebola_virus#cite_note-15http://en.wikipedia.org/wiki/Ebola_virus#cite_note-15http://en.wikipedia.org/wiki/Ebola_virus#cite_note-15http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Cite_pmid.7C_20569424-16http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Cite_pmid.7C_20569424-16http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Cite_pmid.7C_20569424-16http://en.wikipedia.org/wiki/NPC1http://en.wikipedia.org/wiki/Nature_(journal)http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Niemann-Pick_disease,_type_Chttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Marburg_virushttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid22395071-19http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid22395071-19http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid22395071-19http://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-13http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Small_moleculehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid22395071-19http://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866101-18http://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Marburg_virushttp://en.wikipedia.org/wiki/Filovirushttp://en.wikipedia.org/wiki/Virushttp://en.wikipedia.org/wiki/Niemann-Pick_disease,_type_Chttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid21866103-17http://en.wikipedia.org/wiki/Nature_(journal)http://en.wikipedia.org/wiki/NPC1http://en.wikipedia.org/wiki/Ebola_virus#cite_note-Cite_pmid.7C_20569424-16http://en.wikipedia.org/wiki/Ebola_virus#cite_note-15http://en.wikipedia.org/wiki/Sense_(molecular_biology)http://en.wikipedia.org/wiki/Ebola_virus#cite_note-pmid8219816-14http://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Viral_envelopehttp://en.wikipedia.org/wiki/Glycoproteinhttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-BiomarkerDatabase-138/14/2019 EBOLA VIRUS.docx
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The virus attaches to host receptors through the glycoprotein (GP) surfacepeplomer andisendocytosed intomacropinosomes in the host cell
[21]
Viral membrane fuses withvesicle membrane,nucleocapsid is released into thecytoplasm Encapsidated, negative-sense genomic ssRNA is used as a template for the synthesis (3'5')
of polyadenylated, monocistronic mRNAs
Using the host cell's machinery, translation of the mRNA into viral proteins occurs Viral proteins are processed, glycoprotein precursor (GP0) is cleaved to GP1 and GP2,
which are heavily glycosylated. These two molecules assemble, first into heterodimers, and
then into trimers to give the surface peplomers. Secreted glycoprotein (sGP) precursor is
cleaved to sGP and delta peptide, both of which are released from the cell.
As viral protein levels rise, a switch occurs from translation to replication. Using thenegative-sense genomic RNA as a template, a complementary +ssRNA is synthesized; this is
then used as a template for the synthesis of new genomic (-)ssRNA, which is rapidly
encapsidated.
The newly formed nucleocapsids and envelope proteins associate at the host cell's plasmamembrane;budding occurs, destroying the cell.
http://en.wikipedia.org/wiki/Peplomerhttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/Macropinosomehttp://en.wikipedia.org/wiki/Ebola_virus#cite_note-21http://en.wikipedia.org/wiki/Ebola_virus#cite_note-21http://en.wikipedia.org/wiki/Ebola_virus#cite_note-21http://en.wikipedia.org/wiki/Vesicle_(biology)http://en.wikipedia.org/wiki/Nucleocapsidhttp://en.wikipedia.org/wiki/Cytoplasmhttp://en.wikipedia.org/wiki/Viral_sheddinghttp://en.wikipedia.org/wiki/Viral_sheddinghttp://en.wikipedia.org/wiki/Cytoplasmhttp://en.wikipedia.org/wiki/Nucleocapsidhttp://en.wikipedia.org/wiki/Vesicle_(biology)http://en.wikipedia.org/wiki/Ebola_virus#cite_note-21http://en.wikipedia.org/wiki/Macropinosomehttp://en.wikipedia.org/wiki/Endocytosishttp://en.wikipedia.org/wiki/PeplomerTop Related