Ebola causes the symptoms it does because of the types of cells it targets , which include a group of immune cells called dendritic cells that act a bit like the body's security cameras. In their absence, other classes of immune cells are left flying blind—so the virus can replicate rapidly. In addition, Ebola can disrupt cells' ability to make interferon—an anti-viral signaling molecule—and can even cause some immune cells to self-destruct.
When Ebola enters other immune cells, the infection causes blood vessels to weaken and triggers the formation of many tiny blood clots, leading to the hemorrhages and bleeding seen in some, but not all, Ebola cases.
Cells in the liver, adrenal gland, and gastrointestinal tract suffer immensely, throwing an infected person's body into chaos.
Health officials emphasize the importance of preventing contact with Ebola in the first place through hand-washing and avoiding contact with people or animals infected with the virus.
Once a person is infected, treatments center on taking care of the symptoms. Oxygen and intravenous fluids help, as do medications that address diarrhea and blood pressure loss.
The CDC says that the vaccine should become officially licensed by U. In addition, experimental antiviral drugs that can stop Ebola replication in its tracks are under development. The Ebola virus was first formally identified in the fall of , after an outbreak that struck near Yambuku , a village near the Ebola river in the northern Democratic Republic of the Congo then Zaire.
From September 1 to October 24 of that year, villagers succumbed to the fever; about eight out of nine died. Meanwhile, people in Sudan—including 37 percent of a cotton factory's cloth room workers— fell ill to a similar virus , of whom died within weeks of being infected.
Between and , health officials tracked a total of 35 cases in Sudan and the DRC , 23 of which ended in fatalities. In , people in the Philippines and the U. On October 2, , a hundred monkeys were shipped from the Philippines to New York City and were driven to Hazelton Research Products, a company in Reston, Virginia, that kept and sold animals for lab testing. By November 12, 14 monkeys either died or were euthanized after showing signs of hemorrhagic fever.
Concern mounted once tests revealed that the monkeys had some kind of Ebola virus. Four workers at the facility also tested positive for Ebola, one of whom seems to have gotten the virus by accidentally cutting himself with a scalpel while studying a monkey that died of infection. Alarmed, the facility brought in U. Army scientists to stabilize the situation. Without causing panic or a threat to public health, scientists had to quietly euthanize the remaining monkeys and sterilize the facility.
Fortunately, the people exposed to the virus didn't show symptoms. And back in the Philippines , studies of animal handlers showed that while some people had antibodies to the virus, they didn't show symptoms. In , when the same strain of Ebola reared its head at a primate facility in Italy , the humans there were also healthy. This species of Ebola—now called Reston ebolavirus —does not cause any symptoms in humans.
Several years later, in , health officials had to confront the largest Ebola outbreak to date: cases in and around Kikwit, a town in the DRC. Initially, the virus spread among families and hospitals; a quarter of all cases were among health-care workers. The virus can persist in certain body fluids, like semen, after recovery from the illness. Ebola survivors may experience side effects after their recovery. These may include tiredness, muscle aches, eye and vision problems and stomach pain.
Skip directly to site content Skip directly to page options Skip directly to A-Z link. Ebola Ebola Virus Disease. Section Navigation. Facebook Twitter LinkedIn Syndicate. What is Ebola Virus Disease? Biomechanics of how the Ebola virus attaches to its host cell. Retrieved January 12, from www. Featured Content. This study helps understand how the virus uses the host to Researchers are using supercomputers to simulate the inner workings of Ebola as well as COVID , looking at how molecules The findings also suggest that impaired cell adhesion may The findings provide the basis for launching a ScienceDaily shares links with sites in the TrendMD network and earns revenue from third-party advertisers, where indicated.
Print Email Share. No More Annual Flu Shot? Living Well. Several inflammatory mediators are induced within the first hour of EBOV exposure, that is, prior to virus gene expression, suggesting a direct role of the GP present on virion surface in inducing an initial inflammatory response. This newly discovered activation mechanism of non-infected immune cells by shed GP could have an important role in the establishment of systemic inflammation during infection, provoking the excessive cytokine storm that appears to be detrimental to survival after infection.
Although IL was mildly elevated in survivors, probably as a feedback mechanism to control the inflammatory response, the increase was short lived, as would be expected once cytokine levels returned to normal levels. However, IL was 6- to fold higher in fatal cases and remained elevated until death.
As disease progresses, abnormal production of nitric oxide has been shown, 53 inducing several pathological disorders including apoptosis of bystander lymphocytes, tissue damage and loss of vascular integrity, which might contribute to virus-induced shock.
Subsequent extensive viral replication leads to increased levels of additional pro-inflammatory cytokines, which then triggers the coagulation cascade. Moreover, death and hemorrhage were associated with elevated thrombomodulin and ferritin levels. An increase of ferritin was also observed in other viral hemorrhagic fever infections such as Dengue 54 and Crimean Congo hemorrhagic fevers. In one possible model, these cytokines could recruit leukocytes to areas of inflammation, and the production of adhesion molecules, such as ICAM, would facilitate leukocyte adhesion, rolling, and diapedesis.
This would leave an activated, leukocyte-enriched, procoagulant endothelium, causing deregulated hemostasis, which could manifest clinically as hemorrhage. Immature DC function as sentinels of the adaptive immune system. On the other hand, the downstream effects of antigen-presenting cell dysfunction are profound with a marked lack of adaptive immunity noted in fatal cases of filovirus infection. In the context of innate immune response, a decisive role of NK cells in inducing a protective immunity by EBOV-like particle administration was suggested in a mouse model.
It is well known that NK cells have a crucial role for their ability to mediate direct protective cytotoxicity and to drive adaptive immune response by helping DC maturation.
An effective immune response needs the coordinate activities of both humoral and cellular arms. In recovered patients, robust immune responses, with early and increasing levels of IgM and IgG, was developed during the acute phase of EBOV infection, 67 followed by clearance of circulating viral replication markers, although fatal infections were characterized by impaired humoral responses, with absent virus-specific IgG and barely detectable IgM.
Recently a role of heavy glycosylation of the mucin-like domain of viral GP in shielding the cell-free virus from access to potential virus-neutralizing antibodies was described. During Ebola infection, the antibody titer represents the best correlate of protection, 73 , 74 however several evidences suggest a key role of T cells in mediating a protective immune response.
Moreover, DNA fragmentation in blood leukocytes was observed, indicating that massive intravascular apoptosis occurred during the days immediately preceding death.
The ability of EBOV-infected PBMC to induce lymphocyte apoptosis was shown in vitro 35 and confirmed in vivo in mice, 61 in non-human primate animal models 29 and in humans. Respectively, It is well known that T-cell activation needs a coordination of three different signals Figure 4 : i TCR recognition of MHC-peptide; ii binding of several co-stimulatory molecules between DC and T cells; and iii balanced ensemble of soluble factors in the microenvironment.
As well known, this inappropriate interaction induces T-cell apoptosis, thus blocking all T-cell helper functions on CD8-mediated cytotoxicity and the production of antibodies by B cells Figure 4.
The final result is a marked collapse of adaptive immune response. Notably, in a mice model, a residual T-cell function is observed in the remaining cells despite their massive loss in numbers.
Studies carried out, after the Ebola outbreak in Uganda, showed a drastic decrease in the number of circulating T lymphocytes in succumbing people but not in survivors.
Interestingly, despite the large loss of lymphocytes occurring during the infection, no signs of virus infection in lymphocytes could be detected, suggesting a bystander mechanism of apoptosis. The molecular mechanism leading to the apoptosis induction in bystander lymphocytes during the Ebola infection is not defined, however it has been proposed that it results from the activation of several different cell death modalities.
These might include the death receptors pathways mediated by both TNF-related apoptosis-inducing ligand and Fas, stimulated by soluble mediators or possibly by direct interactions between lymphocytes and EBOV proteins. In addition, recent studies have shown that EBOV does not induce apoptosis in infected cells but rather leads to a non-apoptotic form of cell death, that ultrastructural analysis indicates to represent necrotic cell death. Although the classic severe EBOV disease presentation is characterized by hemorrhagic events petechiae, ecchymosis, mucosal hemorrhages and visceral hemorrhagic effusions , studies defining the molecular mechanisms of endothelial impairment are elusive.
The GP has been suggested to have a key role in the induction of cytotoxicity and injury in endothelial cells, which is characterized by cell rounding and detachment associated by downregulating cell-adhesion molecules typical of anoikis. In contrast, the soluble GP does not activate endothelial cells or change the endothelial barrier function.
Over the last decade, the knowledge of cell death signals involved in disease pathogenesis totally changed. Indeed, in addition to apoptosis, multiple forms of regulated necrosis have been shown to have a key role in pathologies such as sepsis, inflammatory diseases and infectious disorders. The liver is another important target for EBOV, 86 , 87 , 88 , 89 probably having an important role in the disease pathogenesis and hepatocellular necrosis have been reported both in patients and in experimental animal models.
Of the microRNAs identified, several were predicted to target genes involved in the DNA damage response, apoptosis and autophagy. Autophagy aids in the removal of pathogens a process called xenophagy by working in conjunction with the innate immune system. Interestingly, both TLRs and type-I IFNs mediate induction of autophagy promoting the autophagosome fusion with pathogen-containing phagosomes leading to the elimination of intracellular pathogens.
Rab 7, a protein involved in transport to late endosomes and in the biogenesis of the perinuclear lysosome compartment, is required for the normal progression of autophagosomes to autophagolysosomes.
In fact, low dose of this compound induce the formation of autophagolysosomes and the accumulation of GFP-LC3 puncta. Future studies should address this hypothesis. At the moment, no approved vaccine or drug is available for Ebola. Experimental vaccines and treatments for Ebola are under development, but they have not yet been fully tested for safety or effectiveness. Current experimental approaches for treatment, or post-exposure prophylaxis of EBOV diseases, are based on: antivirals directly targeting the virus i.
EBOV is able to evade innate and adaptive both humoral and cellular responses by encoding for multiple viral proteins that inhibit both type-I IFNs synthesis and response, by masking viral epitopes by glycosylation processes, by deregulating inflammatory response, by preventing DC maturation, thus resulting in a catastrophic failure of innate and adaptive immunity.
Thus host factors have a key role for viral replication and release, and may represent good targets for therapeutic strategies. Among host factors representing potentially promising targets for anti-Ebola strategies, newly discovered mechanisms may provide a new perspective for elaborating innovative strategies.
In particular, we can take some advantage from the knowledge of cell death in the Ebola pathogenesis to open up the way to new strategies toward the development of antiviral therapeutic approaches. Considering the similarities between the role played by TNF in the pathogenesis of bacterial sepsis and the EBOV infection, it might be possible to envisage the treatment of hemorrhagic fevers with anti-TNF antibodies which are known to protect from sepsis.
Moreover, acute treatment with statins and other immunomodulatory agents e. Another possible attempt would be to prevent cell death and in particular necroptosis. For this it would be very important to test in animal models the effects of necrostatin1 which has been shown to be a potent inhibitor of this form of programmed necrosis. Finally, on the basis of our hypothesis that autophagy can help the host's innate immune response to fight the EBOV infection, the treatment with autophagy inducers such as rapamycin, resveratrol and other compounds should be tested in animal models.
National Center for Biotechnology Information , U. Journal List Cell Death Differ v. Cell Death Differ. Published online May Author information Article notes Copyright and License information Disclaimer. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material.
This article has been cited by other articles in PMC. Facts The knowledge about Ebola-dependent pathogenesis is limited owing to the need of work into biosafety level 4 BSL4 laboratories and this represents a significant barrier for experimental study. Open in a separate window. Figure 1. Virus entry EBOV enter the human body via mucosal surfaces, abrasions and injuries in the skin or by direct parental transmission.
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