A research study by scientists at the University of Texas Medical Branch in Galveston sheds light on how Ebola effectively disables the human immune system. Virologist Alex Bukreyev, UTMB professor and senior author of the study, said the research team engineered versions of the Ebola virus in order to understand its effects on immune system. The findings are described in journal PLOS Pathogens.
Previous research shown how Ebola virus inhibits Interferon mediated immune defense system. Interferons are specialized signaling proteins that are made and released in response to an invasion by a virus or other pathogen, which directly inhibit replication of viral particles in cells. These actions were mediated by two protein regions within the Ebola virus’ structure called interferon inhibiting domains, or IIDs, that prevent the host’s interferons from doing their job thus disabling the host’s immune system defenses.
A focus of current research has been how Ebola gets around the host’s cell-mediated immune response, which is another defense mechanism involving some specialized immune cells that either kill virus-infected cells or secrete antibodies that directly neutralize the virus. Researchers assessed role played by interferon inhibiting domains (IID’s) on cell mediated immunity.
The study used genetically altered strains of the Ebola virus that were designed with one or both of the interferon inhibiting domains disabled to study what they do to the host. The altered viruses were placed on specific types of immune cells isolated from human blood, called dendritic cells, T lymphocytes, B lymphocytes and natural killer cells, as these types of cells are key players in marshaling defenses.
“We found that interferon inhibiting domains work not only in ways previously established, which includes interference in cascades of protective biochemical reactions that occur in cells in response to Ebola that limit infection”, Bukreyev said. “The IID’s also counter the activity of immune cells, including T lymphocytes and natural killer cells that kill virus-infected cells as well as B lymphocytes that secrete antibodies.” “It’s a double edged sword – the IIDs not only block interferon signaling, they also prevent infected cells from activating the cell-mediated arm of the immune response,” said Patrick Younan, research scientist and co-lead author of the paper.
Citation: Lubaki, Ndongala Michel, Patrick Younan, Rodrigo I. Santos, Michelle Meyer, Mathieu Iampietro, Richard A. Koup, and Alexander Bukreyev. “The Ebola Interferon Inhibiting Domains Attenuate and Dysregulate Cell-Mediated Immune Responses.” PLOS Pathogens 12, no. 12 (2016).
Adapted from press release by the University of Texas Medical Branch at Galveston.
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