How Ebola and Marburg viruses battle the immune system

Mohamadzadeh, Mansour; Chen, Lieping; Schmaljohn, Alan L.

doi:10.1038/nri2098

Cited by 128 publications

(116 citation statements)

References 111 publications

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“…GP1,2delta, sGP and ssGP may prevent the neutralizing antibodies from binding GP1,2 on the virus surface, contributing to the immune evasion of the virus. 12 In addition to serving as structural components, the Ebolavirus proteins play multiple roles in the virus life cycle. GP mediates cell entry 13,14 and membrane fusion 15,16 between the virus and the host cell.…”

Section: Introductionmentioning

confidence: 99%

Predictive and comparative analysis of Ebolavirus proteins

2015

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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.

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Section: Introductionmentioning

confidence: 99%

Predictive and comparative analysis of Ebolavirus proteins

2015

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“…Various studies support the assumption that a strong, specific and adaptive immune response is needed to survive from Ebola virus infection, as well as balanced response with respect to both humoral and cell mediated immunity [6,19,42,43]. Several vaccine attempts are in clinical trials now or preparing to; plasmid cocktail coding GP gene of EPOV, SUDV or both as well as NP gene of EPOV were used for vaccination of SUDV, although they were immunogenic at high doses and failed to induce robust cellular immunity.…”

Section: Discussionmentioning

confidence: 99%

“…Ebola virus stimulate immune system and inflammatory response at the same time leading to release of tumor necrosis factor (TNF) and interferon-γ (IFNγ) which in turn can disrupt some body tissues [18,19].…”

Section: Introductionmentioning

confidence: 99%

Multi Epitope Peptide Vaccine Prediction against Sudan Ebola Virus Using Immuno-Informatics Approaches

Abu-haraz¹,

Abd-elrahman²,

Ibrahim³

et al. 2017

Adv Tech Biol Med

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Sudan Ebola virus is single stranded negative sense RNA genome belonging to Filovirus Filoviridae family that causes hemorrhagic fever. There is no treatment or vaccine for it, thus the aim of this study is to design a peptide vaccine using immuoinformatics approaches to analyse the glycoprotein of the all strain of SUDV, to determine the conserved region which is further studied to predict all possible epitopes that can be used as a peptide vaccine. A total of 21 Sudan Ebola virus glycoprotein retrieved from NCBI database were aligned to determine the conservancy and to predict the epitopes using IEDB analysis resource. Three epitopes predicted as a peptide vaccine for B cell (PPPPDGVR, ETFLQSPP, LQSPPIRE). For T cell four epitopes showed high affinity to MHC class I (FLYDRLAST, IIIAIIALL, MHNQNALVC and RTYTILNRK) and high coverage against Sudan and the whole world population. Also in MHC class II, Four epitopes that interact with most frequent MHC class II alleles (FAEGVIAFL, FLRATTELR, FLYDRLAST and FVWVIILFQ) with high coverage against Sudan and the whole world population. We recommend in vivo and in vitro study to prove the effectiveness of these predicted epitopes as a peptide vaccine.

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“…Due to the acute effect on the host immune system, recovery time of EBOV infected individual is a lengthy and complex process. EBOV targets the dendritic cells, monocytes and macrophages during the early stages of infection, while, non-lymphocytic cell types at the later stages [18,19]. As there are no effective vaccines and anti-viral therapies available for EBOV, serious efforts are being taken to develop the same in order to prevent infection and cure the disease [7].…”

Section: Introductionmentioning

confidence: 99%

Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations

Ramaiah

Arumugaswami

2016

VirusDis.

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The current outbreak of Zaire ebolavirus (EBOV) lasted longer than the previous outbreaks and there is as yet no proven treatment or vaccine available. Understanding host immune pressure and associated EBOV immune evasion that drive the evolution of EBOV is vital for diagnosis as well as designing a highly effective vaccine. The aim of this study was to deduce adaptive selection pressure acting on each amino acid sites of EBOV responsible for the recent 2014 outbreak. Multiple statistical methods employed in the study include SLAC, FEL, REL, IFEL, FUBAR and MEME. Results show that a total of 11 amino acid sites from sGP and ssGP, and 14 sites from NP, VP40, VP24 and L proteins were inferred as positively and negatively selected, respectively. Overall, the function of 11 out of 25 amino acid sites under selection pressure exactly found to be involved in T cell and B-cell epitopes. We identified that the EBOV had evolved through purifying selection pressure, which is a predictor that is known to aid the virus to adapt better to the human host and subsequently reduce the efficiency of existing immunity. Furthermore, computational RNA structure prediction showed that the three synonymous nucleotide mutations in NP gene altered the RNA secondary structure and optimal base-pairing energy, implicating a possible effect on genome replication. Here, we have provided evidence that the EBOV strains involved in the recent 2014 outbreak have evolved to minimize the detection by T and B cells by accumulating adaptive mutations to increase the survival fitness.

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How Ebola and Marburg viruses battle the immune system

Cited by 128 publications

References 111 publications

Predictive and comparative analysis of Ebolavirus proteins

Predictive and comparative analysis of Ebolavirus proteins

Multi Epitope Peptide Vaccine Prediction against Sudan Ebola Virus Using Immuno-Informatics Approaches

Ebolavirus evolves in human to minimize the detection by immune cells by accumulating adaptive mutations

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