Studying the immunopathogenesis of Ebola virus disease using flow cytometry

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Abstract

The Ebola virus disease (EVD) has posed a constant threat to public health since it was first identified in 1976. Flow cytometry (FC) is one of the leading methods for studying EVD.

The aim of this review is to examine the features of the immunopathogenesis of the EVD, the study of which has become possible thanks to the use of the FC method.

The use of FC and methods based on FC technology (Luminex xMAP, CyTOF) has revealed facts about the immunopathogenesis of EVD: cytotoxic lymphocytes play a leading role in protecting against infection; dendritic cells are an early target of Ebola virus (EV); elimination of NK cells at an early stage of the disease may be the reason for the host's inability to provide a sustained immune response; “evasion” of the virus from the immune response. Fatal outcomes in EVD are associated with an aberrant innate immune response and suppression of adaptive immunity. The immune response in this case is characterized by a “cytokine storm.” Immunosuppression in EVD is manifested by low levels of circulating cytokines and loss of peripheral T lymphocytes. The key factors for the outcome of the infection are the timing and kinetics of viral replication and the immune response. In those who have recovered from the disease, T-cell activation, proliferation, and the formation of specific antiviral cytotoxicity, cellular and humoral immunity, and immunological memory occur. It has been established that an effective criterion for assessing the antigen-specific T-cell immune response formed upon administration of vaccines against EVD is the proportion of multifunctional T-lymphocytes. The phosphatidylserine receptor TIM-1 plays a central role in the penetration of the virus into the body, its spread, and the development of a “cytokine storm.” Inhibition of intercellular transmission of EV depends on the host protein BST2/teperin/CD317. The flow cytometry method allows the detection of viral particles damaged during the production of the EVD vaccine. Issues related to sample preparation for FC of samples containing EV are discussed.

Using the capabilities of FC, it remains to be studied the innate and adaptive responses of the immune system related to the pathogenesis of the EVD at the level of the whole organism, cells, and molecules.

About the authors

Galina V. Borisevich

48 Central Scientific Research Institute

Author for correspondence.
Email: 48cnii@mil.ru
ORCID iD: 0000-0002-0843-9427

Сand. Sci. (Biol.), senior researcher

Russian Federation, Sergiev Posad

Aleksander V. Ovchinnikov

48 Central Scientific Research Institute

Email: 48cnii@mil.ru
ORCID iD: 0000-0003-2309-3572

Cand. Sci. (Tech.), senior researcher

Russian Federation, Sergiev Posad

Svetlana L. Kirillova

48 Central Scientific Research Institute

Email: 48cnii@mil.ru
ORCID iD: 0000-0003-1245-9225

Dr. Sci. (Biol.), leading researcher

Russian Federation, Sergiev Posad

Anna S. Turavinina

48 Central Scientific Research Institute

Email: 48cnii@mil.ru
ORCID iD: 0009-0000-5662-6799

laboratory researche

Russian Federation, Sergiev Posad

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