Predictive and comparative analysis of Ebolavirus proteins

Abstract

Ebolavirus is the pathogen for Ebola Hemorrhagic Fever (EHF). This disease exhibits a high fatality rate and has recently reached a historically epidemic proportion in West Africa. Out of the 5 known Ebolavirus species, only Reston ebolavirus has lost human pathogenicity, while retaining the ability to cause EHF in long-tailed macaque. Significant efforts have been spent to determine the three-dimensional (3D) structures of Ebolavirus proteins, to study their interaction with host proteins, and to identify the functional motifs in these viral proteins. Here, in light of these experimental results, we apply computational analysis to predict the 3D structures and functional sites for Ebolavirus protein domains with unknown structure, including a zinc-finger domain of VP30, the RNA-dependent RNA polymerase catalytic domain and a methyltransferase domain of protein L. In addition, we compare sequences of proteins that interact with Ebolavirus proteins from RESTV-resistant primates with those from RESTV-susceptible monkeys. The host proteins that interact with GP and VP35 show an elevated level of sequence divergence between the RESTV-resistant and RESTV-susceptible species, suggesting that they may be responsible for host specificity. Meanwhile, we detect variable positions in protein sequences that are likely associated with the loss of human pathogenicity in RESTV, map them onto the 3D structures and compare their positions to known functional sites. VP35 and VP30 are significantly enriched in these potential pathogenicity determinants and the clustering of such positions on the surfaces of VP35 and GP suggests possible uncharacterized interaction sites with host proteins that contribute to the virulence of Ebolavirus.

The first complete genomes of Metalmarks and the classification of butterfly families

“…Butterflies are well-suited for such work because they are diverse in colors, patterns and shapes, their genomes are of moderate size and they are closely related to the model organism: Drosophila . Genomes have been reported for five (out of six) butterfly families: the swallowtails (Papilionidae) (Cong et al, 2015a; Li et al, 2015; Mallet, 2015), the Whites and Sulphurs (Pieridae) (Cong et al, 2016a), the Blues (Lycaenidae) (Cong et al, 2016b), the Brushfoots (Nymphalidae) (Ahola et al, 2014; Heliconius Genome, 2012; Zhan et al, 2011), and the Skippers (Hesperiidae) (Cong et al, 2015b). The Brushfoots include Heliconius and the Monarch ( Danaus plexippus ), which are the most thoroughly studied (Nadeau et al, 2014; Zhan et al, 2014).…”

Mapping the clinical outcomes and genetic evolution of Ebola virus in Sierra Leone

“…Lineage SL3 was first detected in late May 2014 and became dominant in July 2014 through continuous expansion and diversification. From the diversified SL3 lineages, 3 lineages (SL3.1.2, SL3.2.4, and SL3.2.5) were shown to be more widespread (12,23, and 18 chiefdoms, respectively) and to possibly infect more patients (53, 82, and 79 viruses, respectively, were identified from the patients). These 3 lineages would be the dominant viruses in the latter months of the outbreak in Sierra Leone in 2014 (Supplemental Figure 2).…”

“…Among these possible fixed substitutions, the number of nonsynonymous mutations (n = 14) was nearly 60% of that of synonymous (n = 23) and noncoding (n = 23) mutations. Notably, 5 of 14 nonsynonymous substitutions (at sites 16679, 16895, 16958, 17848, and 18143) were in the mRNA-capping methyltransferase domain of the L protein (12). Three amino acid mutations (sites 6283, 6726, and 7148) were in the GP1 domain of the GP protein, which affects the attachment to host cells (13).…”

Interplay Among Constitutes of Ebola Virus: Nucleoprotein, Polymerase L, Viral Proteins

“…71 Several possible key di®erences on L have been proposed by comparative analysis between Zaire and Reston or other ebola species. 31,48,72 We mapped out the position of certain key residues: L283V, Y312F, A326S, T330D, S343Y, E350D, T361S, L365F in the binding core with VP35, and R654H, E689S, D759G in the Rdrp domain (listed in Table S2) on 3D model of its protein domain (Fig. 4).…”

“…30 Additional studies further review that GP variations alone are not enough to explan the virulence of ebola Zaire. [31][32][33] Importantly, multiple other studies have suggested that NP and L are most likely the other two major determinants of the pathogenicity/virulence of Ebola viruses. 32,[34][35][36][37] Evidence associated with the outbreak is further extended by computational studies: Hoenen et al 38 analyzed the rate of evolution for Zaire virus; Olabode et al…”