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.

[Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages.

[Functional activity of peritoneal macrophages in experimental Ebola fever].

The phagocytic activity of peritoneal macrophages (a representative of mononuclear phagocytes) as well as the TNF-alpha were studied in animals with different susceptibility to Ebola virus (EV). The results denote the following: 1. Phagocytosis activation by peritoneal macrophages after EV is introduced into the body correlates directly with a susceptibility degree of an animal to EV.

[Strain differences related to Ebola virus reproduction in peritoneal macrophages and in aorta explants of guinea pigs].

Reproduction of the Ebola strains (ES) virus causing lethality in guinea pigs as well as in peritoneal macrophages and aorta explants of animals was investigated in vitro and in vivo; besides, production of interferon-gamma (IFN-gamma) and of tumor necrosis factor-alpha (TNF-alpha) by macrophages and endotheliocytes of guinea pigs was also studied. The interplay "macrophage--ES" by the example of 2 models of susceptibility to ES demonstrates that the ES lethality is not unambiguously related only with a level of virus reproduction in macrophages. The interplay "endotheliocyte--ES" is indicative of that the ES lethality is inversely dependent on a level of production of the IFN-gamma and of TNF-alpha by endotheliocytes.