Genetic factors of Ebola virus virulence in guinea pigs.
Zaire ebolavirus (ZEBOV) causes severe hemorrhagic fever in primates, whereas in guinea pigs it induces a nonlethal infection with a mild fever and subsequent recovery. We performed 7 selective passages in guinea pigs resulted in obtaining of guinea pig-adapted strain (GPA-P7) strain. By the 7th passage, the infection with EBOV induced a lethal disease in animals accompanied by the characteristic hematological changes: leukocytosis (primarily due to neutrophilia) as well as pronounced deficiencies in platelets, lymphocytes, monocytes and significant decrease of blood neutrophils phagocytic capacity. Increasing of virulence correlated with appearance of several nucleotide substitutions: in the genes NP, A2166G (N566S), VP24, U10784C (L147P), G10557A (M71I), G10805U (R154L), and L, G12286A (V236I). It has been theoretically calculated that the mutations associated with an increase in EBOV virulence can confer characteristic secondary structure on the proteins NP (C-terminal region) and full-sized VP24.
Subbotina
Ekaterina
E
Department of Molecular Virology, State Research Center of Virology and Biotechnology Vector, Koltsovo, 630559, Russia. Subbotina@ngs.ru
Dadaeva
Alexandra
A
Kachko
Alla
A
Chepurnov
Alexander
A
D000220:Adaptation, Biological; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D004252:DNA Mutational Analysis; D029043:Ebolavirus / Q000235:genetics* / Q000472:pathogenicity*; D006168:Guinea Pigs; D019142:Hemorrhagic Fever, Ebola / Q000473:pathology / Q000662:veterinary* / Q000821:virology; D007958:Leukocyte Count; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D012692:Serial Passage; D016019:Survival Analysis; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics*
D012367:RNA, Viral; D014764:Viral Proteins; D037521:Virulence Factors