Ebola virus is a rather simple virus. Unlike our cells which transcribe and create thousands of different proteins, the Ebola virus encodes seven structural proteins and one non-structural protein. As mentioned in part 1 of this blog, with upwards of 90 percent of patients succumbing to their infection (depending on the strain), an unknown natural reservoir and a lack of a vaccine, this virus has the potential to cause a severe havoc should a large scale epidemic occur.
Ebola virus infection presents with a high fever and hemorrhage (thus explaining its other name Ebola hemorrhagic fever). The high case fatality has been attributed to several virulence factors including a glycoprotein which kills the innermost cell lining of vasculature (endothelial cells) leading to profuse exsanguination both internally and externally. Severe thrombocytopenia (decreased platelet count -- platelets are necessary for clot formation) further contributes to the uncontrolled bleeding in infected patients.
Two other virus-produced glycoproteins inhibit the induction and action of interferon -- Interferon is an integral component of the immune systems which mediates defence against viral infections. On top of it all, not only do we lack a vaccine, but there are also no current FDA approved antivirals for those infected, limiting treatment to supportive care.
Fortunately, the virus is not considered an aerosol transmitted diseases, emphasizing the need for effective preventative measures during potential outbreaks. When exposed however, the virus is highly infective, and until recently, the mechanism behind how the virus infiltrates host cells had not been established.
In a recent article published in the journal Nature, scientists believe that they identified the protein which permits viral entry into host cells -- a protein called NPC-1. The study demonstrates that cells which had mutated and ineffective NPC-1 proteins failed to become infected by either Ebola virus or its very close relative Marburg Virus (Filoviridae family).
The protein is named after the NPC-1 gene that was discovered in patients with the inherited disorder Niemann-Pick disease type C. Though some patients may live into their adult years (depending on the type), individuals with Niemann-Pick disease generally have a drastically reduced life expectancy. The discovery of the attachment site is important as it provides scientists with a potentially exploitable tool for preventing host infection by the virus. What is even more interesting is that the authors also describe how imipramine (a tricyclic antidepressant) may exert some blockade of the NPC1 protein and had shown to "potently inhibit viral infection" in their tests.
Surely further research will ensue, and should these findings be confirmed, this represents not only a significant step in our understanding of Ebola virus infectivity but also presents an opportunity to develop therapeutics should another outbreak occur.