Zaire ebolavirus

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Classification

Higher order taxa

Group: Group; V ((-)ssRNA) Order; Mononegavirales Family; Filoviridae Genus; ebolavirus Species; Zaire

Species

NCBI Taxonomy: [4]

Zaire ebolavirus

Description and significance

The Zaire ebolavirus is filamentous in shape and structure(NIH, 2010)[1]

The appearance of this negative sense single stranded RNA (nonsegmented) virus is filamentous in structure(NIH, 2010)[5]. This virus was discovered in the Democratic Republic of Congo and is a species of the Genus ebolavirus. The Genus ebolavirus contains five different species. The five species are: Sudan ebolavirus (SEBOV), Reston ebolavirus (REBOV),Bundibugyo ebolavirus (BEBOV), Ivory Coast ebolavirus (CIEBOV), and Zaire ebolavirus (ZEBOV)(NIH, 2010)[6]. They were all discovered around 1976 with only one strain that is not pathegenic in humans which is the Reston ebolavirus. The filoviruses can cause up to a 90% mortality rate in humans as well(NIH, 2010)[7]. The virus is not considered to be living due to the fact that without a host the virus will die, although this topic is highly controversial.

Genome structure

The complete genome is 18,959 base pairs which makes up a linear strand of RNA. This is a single stranded, nonfragmented, negative sense RNA, which resides in Group V of the Baltimore classifcation system. This class of viruses needs a RNA-dependent RNA polymerase to transcribe the negative sense strand in to a positive sense strand. This can only be conducted by a viral RNA-dependent RNA polymerase. The Zaire Ebola virus consists of 7 linearly arranged genes. The order of the genes is as follows: 3'-NP-VP35-VP40-GP-VP30-VP24-L. The transcriptional start and stop signals contain the sequence 3′-UAAUU. Three base intergenic sequences are present between the NP and VP35 genes (3′-GAU) and VP40 and GP genes (3′-AGO, and a large intergenic sequence of 142 bases separates the VP30 and VP24 genes. Stem-and-loop structures were identified in the 5I end of the leading strand. Alignment of predicted amino acid sequences showed that the structural proteins of Ebolavirus and Marburgvirus contain large regions of homology.

Cell structure and metabolism

VP30, VP35, nucleoprotein, and a polymerase protein [L] are the 4 virion structural proteins. VP40, glycoprotein [GP], and VP24 are the 3 membrane-associated proteins. The surface GP is encoded in 2 open readingframes (ORFI and ORFII). ORF I (amino-terminal) encodes for a small (50-70 kd), soluble, nonstructural secretory glycoprotein (sGP) that is produced in large quantities early in Ebola infection. The sGP binds to neutrophil CD16b, a neutrophil-specific Fc g receptor III, and inhibits early neutrophil activation. This could account for the lymphopenia associated with an Ebola infection. According to this research sGP is likely the key factor in preventing a successful immune response from the host. However, more recent research has proven that neutrophils do not express a specific receptor for Ebolavirus sGP. It is unlikely that sGP plays a role in the Ebolavirus pathogenesis through interfering with the innate immunity by targeting neutrophils, so the exact metabolism of the Ebolavirus is still unknown.

Ecology

Zaire ebolavirus RNA has been discovered within the cells of rodents and shrews that occupy niches in forest areas. This concludes that reservoirs of this virus are found in Central African Republic inside the rodent's internal organs. It has started a recent epidemic in the Republic of Congo, originally called Zaire, which has lead to a sudden death in mammals and humans. This zoonotic pathogen can be transmitted from animals to other uninfected animals and jump to invade humans. Zaire ebolavirus is a parasite to humans; therefore, the symbiosis is a parasitism relationship. The virus benefits and the host is negatively impacted during their interaction. This Zaire ebolavirus is found within mammals that consume the natural vegetation of the forest environment of Africa. This negatively impacts wildlife like apes, chimpanzees, and bats. Once transferred to human, this becomes a devastation to public health.

Pathology

The Zaire ebolavirus VP35 protein which has specific sites in order to bind to dsRNA[2]

Out of any species of the Ebolavirus, the Zaire species is by far the most lethal. The fatality rate can reach up to 90% in some cases and death occurs within days of the initial infection[8]. The symptoms include: shock, fever, and internal coagulation which can determine how rapidly the virus is replicated. The host is usually human, however the virus can be spread to primates. There is a protein called the Ebola viral protein 35 (VP35) which is a cofactor for the Ebola RNA polymerase and this complex is needed for viral production[9]. The virulence factor for the Zaire ebolavirus is when VP35 binds to double strand RNA (dsRNA). Recently, an end-cap was discovered for the VP35 protein, which are hydrophobic molecules attached to the end tail. This end-cap actually helps the VP35 protein bind to dsRNA[10]. This end-cap can also mimic the espression of RlG-l-Like receptors (RLR) which is one of the reasons the virus is so successful in taking down the hosts immune system. The VP35 protien is a great target when treating the Ebolavirus[11]. There have been two different methods tested which are by using nucleic acids and siRNA molecules.

This is the FGI-103 molecule used in the successful protection of mice from ZEBOV[3]


When the immune system first reacts to the Zaire ebolavirus, a large quantiy of chemokines, cytokines, and growth factors are produced by the body. Also, it was noted that there is lymphocyte apoptosis due to the apparent loss of peripheral CD4 and CD8 lymphocytes[12]. Thus, it is easy for the virus to take over other cells if the lymphocyte production is low. In another study using a mouse strain of the Zaire ebolavirus, the treatment using FGI-103 proved to be an efficient way to protect the mice[13]. For the 10 control mice, the typical 90% mortality rate was observed. However, for the 10 mice that received 10mg/kg of FGI-103 after 1,000 PFU ZEBOV, they were protected and were healthy after 10 days[14]. This study is promising in finding a treatment for Zaire ebolavirus while also keeping the mortality rate down.

Current Research

The Zaire ebolavirus is a deadly infectious pathogen that can suppress the immune system. It has a case-fatality rate of 90% in patients who are infected due to a lethal hemorrhagic fever syndrome. This Zaire ebolavirus is confirmed infected patients blood by the presence of a specific non-self antigen. This virus attacks the adaptive immune response by decreasing the amount of B lymphocytes and T lymphocytes present. These B cells and T-cells such as CD4 and CD8 lymphocytes are necessary to produce cytokines as immune mediators. Patients who die within a couple days show a decrease in of B and T cells numbers due to apoptosis, cell programmed death. T cell are necessary to be activated to kill off virus infected cells. Researchers have been trying to make a vaccine to cure this disease. They have performed in vitro studies with mice by injecting them with a strain and Zaire ebolavirus and performing assays on cytokines and detecting by fluorescence for final concentrations. These have provided consistent results for further studies. (Wauquier et al 2010).

Cool Factor

Zaire ebolavirus can potentially be used as a bioweapon due to its lethal effect on humans. There is a serious movement conducted by scientists in order to create a treatment for this virus, in case it were to ever be used as a weapon. The virus has also been the star in many fictional works, such as The Hot Zone by Richard Preston.

References

[15]."Electron Micrograph of Zaire ebolavirus." Photograph. BBC. First Last. London: BBC NEws, 1997. Web. 24 Oct 2011.

[16] Feldmann H, Wahl-Jensen V, Jones S, and Stroher U (2004). Ebola Virus Ecology: A Continuing Mystery.Trends in Microbiology.Vol 12(10):433-437.

[17] Leung, D. W., Prins, K. C., Basler, C. F., & Amarasinghe, G. K. (2010). Ebolavirus vp35 is multifunctional virulence factor. Virulence, 1(6), 526-531. doi: 10.4161/viru.1.6.12984

[18] NCBI Taxonomy Zaire ebolavirus

[19] National Institutes of Health. "Botulinum Neurotoxin, B. Anthracis and Variola Virus" 'National Academies Press'. 2010

[20] Olejnik, J., Ryabchikova, E., Corley, R.B, and Mühlberger, E. "Intracellular Events and Cell Fate in Filovirus Infection", 'Viruses'. 2011. Volume 8. p.1501-1531

[21] Sanchez, Anthony, Kiley, Michael P, Holloway, Brian P, Auperin, David D. (1993). Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus. Virus Research Vol. 29(3): 215-240.

[22] Sanchez A, Trappier SG, Mahy BW, Peters CJ, Nichol ST (1996). The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing. Proc Natl Acad Sci U S A. Vol. 93(8):3602-3607.

[23] Sui, Jianhua, Marasco, Wayne A. (2002). Evidence against Ebola Virus sGP Binding to Human Neutrophils by a Specific Receptor. Virology. Vol. 303(1): 9-14.

[24] Volchkov,V.E., Volchkova,V.A., Chepurnov,A.A., Blinov,V.M., Dolnik,O., Netesov,S.V. and Feldmann,H. "'Zaire ebolavirus', 'Characterization of the L gene and 5' trailer region of Ebola virus'". 'Journal of General Virology'. 1999. Volume 80. p.355-362

[25] Wauquier N., Becquart P, Padilla C, Baize S, Leroy E (2010) Human Fatal Zaire Ebola Virus Infection Is Associated with an Aberrant Innate Immunity and with Massive Lymphocyte Apoptosis. Public Library of Science Vol. 4(10):837-847

[26] Warren, T.K, Warfield, K.L, Wells, J., and Enterlein, S. "Antiviral Activity of a Small-Molecule Inhibitor of Filovirus Infection", 'Antimicrobial Agents and Chemotherapy'. 2010. Volume 54. p.2152-2159


Edited by student of Iris Keren