Ebola+Virus+Primary+Research

Primary Article

Folarin et al. presents a model for genomic tracing of an outbreak using a well-known and contained infected population. Using the clinical and genomic data they support the conclusion from contact tracing that transmission to Nigeria occurred through a single lineage and transmission from Nigeria to elsewhere did not occur. This result is shown below in the phylogenetic tree generated by the study, taken with permission.

Current State of the Field

 There are 309 complete genomes of the viruses in the //Ebolavirus// genus. Within those 309 complete genomes on file, there are 248 complete genomes for //Zaire ebolavirus// and of that amount 181 complete genomes come from the West African outbreak according to Virus Pathogen Resource or ViPR. That means the West African outbreak generated nearly 60% of all the genetic information for this genus and more than 75% or the //Zaire ebolavirus//. Of all the genomes of //Zaire ebolavirus//, there are only two confirmed cases of the host being non-human.

 The only documented non-human to human transmission of the Ebolavirus genus occurred in 2009, where pigs in the Philippines were infected with Reston Virus and the pig farmers had antibodies present for Reston Virus. In Weingartl et al. transmission of //Zaire ebolavirus,// or Ebola Virus, had its limitations and challenges for research. The pigs were inoculated oro-nassally and Macaques primates were exposed indirectly through the pig’s environment. The infected Macaques were not able to transmit the virus to other Macaques without the exposure to the pig’s environment. This research pioneered experimental interspecies virus transmission.

 The relationship between interspecies transmissions is further illuminated with Pappalardo et al. Here researchers examined and compared genomic data of Reston Virus and Zaire ebolavirus, in silico. They revealed possible protein-protein interactions that could explain human pathogenicity, since Reston Virus is non-pathogenic to humans. Some of their changes in protein-protein interactions include VP24, VP30 and VP40. VP30 is a dimer structure, in Ebola R262 is part of the dimer interface and forms a hydrogen bond with the backbone of residue 141 in the other subunits. In Reston virus, A262 does not form a hydrogen bond and is not involved with the interface of VP30. This creates a destabilizing factor that is estimated around ΔG= -0.969 Kcal/mol. These differences are shown in Figure 2 taken from the research of the study with permission.

 VP40 exists in three known oligomeric forms. Dimeric VP40 is responsible for trafficking to the protein to the cellular membrane. Hexameric VP40 initiates budding and forms filamentous structures. Octameric VP40 regulates viral transcription by binding to RNA and has the greatest impact in determining virulence. There are two significant determining positions that are located at an S-G-P-K beta turn in Ebola, the proline at position 85 confers backbone rigidity. In the Reston virus, threonine replaces proline in this position and introduces backbone flexibility and a side chain that can form hydrogen bonds. This change can affect octamer stabilization. The second significant determining position in VP40 is in alpha helix five, in Ebola glutamine 245 is replaced by a proline in the Reston Virus. This structural change greatly influences the VP40 stability between two alpha helices. Proline is not an amino acid that is usually found in alpha helices. This creates an inherent instability by breaking and shortening alpha helix five and destabilizing the hydrophobic core. This proline position is shown in yellow of the VP40 octamer in Figure 3, taken from the study with permission.

VP24 VP24-mediated inhibition of interferon signaling may be critical to species-specific pathogenicity (Pappalardoet al. 2016). Adaptation specific VP24 mutations in rodents are located in the KPNA5 binding site. These mutations include T131S, M136L and Q139R (Pappalardoet al. 2016).

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