Conserved differences in protein sequence determine the human pathogenicity of Ebolaviruses

Autor: Morena Pappalardo, Miguel Juliá, Mark J. Howard, Martin Michaelis, Mark N. Wass, Jeremy S. Rossman
Jazyk: angličtina
Rok vydání: 2015
Předmět:
0301 basic medicine
Models
Molecular
alpha Karyopherins
Protein Conformation
Swine
Virulence Factors
Ciències de la salut::Medicina [Àrees temàtiques de la UPC]
SDPs
Ebola virus disease
Biology
medicine.disease_cause
Reston viruses
Airborne transmission
Genome
Virus
Article
Host Specificity
Conserved sequence
Viral Matrix Proteins
03 medical and health sciences
Viral Proteins
VP40
medicine
Animals
Humans
Amino Acid Sequence
Sudan viruses
Genètica vírica
Malaltia de l'Ebola
Informàtica::Arquitectura de computadors [Àrees temàtiques de la UPC]
Conserved Sequence
Phylogeny
Ebolavirus
Swine Diseases
Multidisciplinary
Viral matrix protein
Specificity determining positions
Taϊ Forest viruses
Genetic Variation
Alpha Karyopherins
Hemorrhagic Fever
Ebola
Virology
030104 developmental biology
High performance computing
Ebola viruses
Bundibugyo viruses
Càlcul intensiu (Informàtica)
Viral genetics
Zdroj: UPCommons. Portal del coneixement obert de la UPC
Universitat Politècnica de Catalunya (UPC)
Scientific Reports
Popis: Reston viruses are the only Ebolaviruses that are not pathogenic in humans. We analyzed 196 Ebolavirus genomes and identified specificity determining positions (SDPs) in all nine Ebolavirus proteins that distinguish Reston viruses from the four human pathogenic Ebolaviruses. A subset of these SDPs will explain the differences in human pathogenicity between Reston and the other four ebolavirus species. Structural analysis was performed to identify those SDPs that are likely to have a functional effect. This analysis revealed novel functional insights in particular for Ebolavirus proteins VP40 and VP24. The VP40 SDP P85T interferes with VP40 function by altering octamer formation. The VP40 SDP Q245P affects the structure and hydrophobic core of the protein and consequently protein function. Three VP24 SDPs (T131S, M136L, Q139R) are likely to impair VP24 binding to human karyopherin alpha5 (KPNA5) and therefore inhibition of interferon signaling. Since VP24 is critical for Ebolavirus adaptation to novel hosts and only a few SDPs distinguish Reston virus VP24 from VP24 of other Ebolaviruses, human pathogenic Reston viruses may emerge. This is of concern since Reston viruses circulate in domestic pigs and can infect humans, possibly via airborne transmission.
Databáze: OpenAIRE
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