EBOLA VIRUS.docx

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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_disease


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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


124/97 (78%)

2002 Ogoou-Ivindo Province,Gabon;Cuvette-Ouest


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-13


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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/Peplomer

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