Modeling of the Ebola virus delta peptide reveals a potential lytic sequence motif.

William Gallaher,Robert Garry

doi:10.3390/v7010285

Abstract

Filoviruses, such as Ebola and Marburg viruses, cause severe outbreaks of human infection, including the extensive epidemic of Ebola virus disease (EVD) in West Africa in 2014. In the course of examining mutations in the glycoprotein gene associated with 2014 Ebola virus (EBOV) sequences, a differential level of conservation was noted between the soluble form of glycoprotein (sGP) and the full length glycoprotein (GP), which are both encoded by the GP gene via RNA editing. In the region of the proteins encoded after the RNA editing site sGP was more conserved than the overlapping region of GP when compared to a distant outlier species, Tai Forest ebolavirus. Half of the amino acids comprising the “delta peptide”, a 40 amino acid carboxy-terminal fragment of sGP, were identical between otherwise widely divergent species. A lysine-rich amphipathic peptide motif was noted at the carboxyl terminus of delta peptide with high structural relatedness to the cytolytic peptide of the non-structural protein 4 (NSP4) of rotavirus. EBOV delta peptide is a candidate viroporin, a cationic pore-forming peptide, and may contribute to EBOV pathogenesis.

Highlights

Filoviruses, first discovered in 1967, are associated with severe febrile illness in humans and non-human primates [1,2,3]
Delta Peptide is Differentially Conserved amongst Otherwise Disparate Ebolavirus Glycoproteins
It was observed that five mutations in GP1, relative to the 1976 reference sequence, are in the region of the protein encoded by the portion of the mRNA after the RNA

Summary

Introduction

Filoviruses, first discovered in 1967, are associated with severe febrile illness in humans and non-human primates [1,2,3]. Native to the middle and southern areas of Africa, in March of 2014, it became apparent in the West African country of Guinea that an outbreak of Ebola Virus Disease (EVD) had begun caused by a virus with similarities to those that had earlier appeared only in Middle. EVD has since spread across several West African countries, most prominently in Guinea, Sierra Leone and Liberia, and as of early January 2015 had reached over 20,000 total cases with over 7500 deaths [7]. While a few exported cases from the current ongoing outbreak have been reported and quickly contained in Western countries far, the virus constitutes a threat of arriving undetected in locations outside of West Africa [8,9,10]. The viral genome codes for seven proteins, which are found in infectious virus particles

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