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Overview of Ebola Virus

Ebola virus belongs to the Filoviridae family can cause epidemics of haemorrhagic fever with high case-fatality rates. Ebolavirus first appeared in 1976 in 2 simultaneous Ebola outbreaks, in Nzara, Sudan, and in Yambuku, Democratic Republic of Congo. Ebola virus (EBOV) cause a severe viral hemorrhagic fever with high mortality in humans and nonhuman primates, killing up to 90% of those infected. The disease is characterized by widespread petechial hemorrhages, focal necrosis of the liver, kidney, and spleen, shock, and ultimately, death. Despite considerable effort, no animal or arthropod reservoir capable of sustaining the virus between outbreaks has been identified. Moreover, the pathogenesis of Ebola hemorrhagic fever is not fully understood, and no Ebola virus vaccine or effective therapies are currently available. Ebola virus (EBOV) is a select agent, World Health Organization Risk Group 4 Pathogen.

Based on antigenicity and the nucleotide sequences, the genus Ebolavirus is considered to have five species. Four of them have caused Ebola virus disease in human:Zaire Ebolavirus( ZEBOV / EBOV), Sudan eoblavirus (SUDV / SEBOV); Taï Forest ebolavirus (formerly Côte d'Ivoire ebolavirus, abbreviation:TAFV / CIEBOV) and Bundibugyo ebolavirus (BDBV / BEBOV). The last one Reston ebolavirus (REBOV / RESTV) have cause disease in nonhuman primates. But now, the Reston eoblavirus (RESTV) species, found in Philippines and the People's Republic of China, can infect humans, but no illness or death in humans from this species has been reported to date. Meanwhile, Bundibugyo ebolavirus (BDBV),Zaire ebolavirus (ZEBOV), and Sudan eoblavirus (SUDV) have been associated with large Ebola virus Disease / Ebola hemorrhagic Fever (EVD / EHF) outbreaks in Africa, whereas Reston eoblavirus (RESTV) and Taï Forest ebolavirus (TAFV) have not.

Picture below has shown the geographic distribution of Ebola virus disease outbreaks in human and animals in 2014. (From WHO)

Ebolavirus Ebolavirus
Ebolavirus

After infected with Ebolavirus for 1-2 weeks, patients will suffer fever, asthenia, diarrhoea, abdominal pain, headache, arthralgia, myalgia, sore throat, dysphagia, and conjunctivitis. These are type Ebola virus symptoms after Ebola virus infection. One week later, they will get a rash, and subsequently the haemorrhagic complications, which usually result in death in 10 days. For the survivors, severe asthenia, hearing loss, ocular signs may affect them for 2 weeks to 2 months until recovery. No vaccine exists and there is no FDA-approved therapeutics. Thus, Ebola virus has been considered as a biosafety level 4 pathogen. The case fatality rate of Ebola virus disease varies depending on the ebolavirus species involved, with Ebola virus (EBOV) having a case fatality rate of 60-90%, whereas Sudan ebloavirus (SUDV) and Bundibugyo ebolavirus (BDBV) show lower average case fatality rates of 40-60% and 25%, respectively. Taï Forest ebolavirus (TAFV) has caused only a single severe infection in humans; therefore, the lethality rate is unknown.

Ebola virus genome

The Ebola virus (EBOV) contains a linear, single-stranded, negative-sense RNA genome which is approximately 19 kb in length. It encodes seven structural proteins and a non-structural protein. Structural proteins are nucleoprotein (NP), polymerase cofactor (VP35), (VP40), GP, transcription activator (VP30), VP24, and RNA polymerase (L). The characteristic of Ebola virus genome is that the 3'terminus is not polyadenylated and the 5'end is not capped.

The nucleotide sequences of the 3' and 5' terminuses are complementary to each other. The nucleotide sequence coding 3' leader is conserved in genera of same family. For the 5' terminus, neither covalently attached terminal protein nor cap exists. Since there are initiation and termination signals in intergenic regions, transcription of the genome ssRNA could produce about nine individual mRNAs. The sequences of GP vary among species with a range from 37% to 41%, therefore, it could be used for the phylogenetic analysis of Ebola virus (EBOV). Moreover, two forms of GP protein with different lengths can be expressed during Ebola virus infection, including the peplomer GP1,2 and the secreted sGP. The GP1,2 containing disulfide-linked subunits GP1 and GP2 locates in the viral membrane and forms the spikes on virion surface. The C-terminally truncated sGP is produced through RNA editing, and it contains a N-terminal 295 residues that is identical to GP1,2.

Ebolavirus

Ebola virus structure

The EBOV virion is filamentous, pleomorphic with extensive branching or U-shaped or 6-shaped with a diameter around 80 nm and a variable length up to 1400 nm. It is enveloped by lipid bilayer, with anchored glycoprotein GP forming the viral spikes on the surface. It contain a single linear RNA molecule, nucleoprotein (NP), nucleocapsid viral protein 30 (VP30), VP35, and polymerase (L) in the core. Matrix proteins VP24 and VP40 are present in the space between the core and envelope.

Ebola virus replication

Trimers of Ebola virus GPs on virions interact with both attachment factors (C-type l ectins) and receptors (TIM-1) on the surface of permissive cells. Attachment factors are likely to co ncentrate virions on cells before receptor engagement and virion internalization by macropinocytosis. Macropinocytosis is enhanced by tyrosine kinase receptors such as TAM family members. Following endosomal acidification, Cathepsins L and B trim the Ebola virus GP to a smaller form that needs at least one as yet undetermined factor to elicit GP fusion with host endosomal membranes. This smaller form of GP is able to interact with both TIM-1 and the endosomal portion of the NPC1 protein; however, whether GP and TIM-1 interact within endosomes is not known. The energetically unfavorable insertion of the EBOV GP2 fusion loop into host endosomal membranes (i) is followed by the energetically favor able collapse of Ebola virus GP into a six-helix bundle (ii ) allowing for lipid mixing and hemifu sion of host and viral membrane lipids (ii). Finally, the hemifused host and vira l membranes resolve and a complete pore is formed (iii) through which the viral genomic complex passes into the cytoplasm, allowing the viral replication cycle to continue.

Ebolavirus Replication

Ebola virus Related Studies

    1. Catherine L. Hunt et al. (2012). Filovirus Entry: A Novelty in the Viral Fusion World. Viruses.4, 258-275.
    2. Jason S. Richardson, et al.. (2010). Recent advances in Ebolavirus vaccine development.Human Vaccines 6:6, 439-449.
    3. Gatherer D,et al.. (2014).The 2014 Ebola virus disease outbreak in West Africa.J. Gen. Virol. 95, 1619–1624.
    4. Thomas Hoenen,et al.. (2012).Current Ebola vaccines.Expert Opin Biol Ther. 12(7): 859–872.
    5. B. Le Guenno,et al.. (1997).Ebola virus.Bull. Inst. Pasteur. 95, 73-83.
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