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Matt, Pathogenesis Specialist


Pathogenesis & Recombinant Virus Specialist, & Social Chaos Theorist

Ebola: Virulence, Symptoms & Causes, & Protein Pathogenicity

Virulence Factors

The Ebola virus, one of two types of filovirus, comes in four different forms, Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast and Ebola-Bundibugyo, that are potentially harmful, and one, the Ebola-Reston, which currently only infects primates.  All four of the subtypes have similar factors of virulence, being spread initially through an unknown vector, though research possibly indicates that it is initially spread via zoonoses, or contact with an animal carrier (primates are a prime suspect), and then is transmitted via human contact with infected victim's blood, secretions, organs, or other bodily fluids.  Unfortunately, the natural reservoir of Ebola has not been identified yet, and as such, not much progress towards attenuating the virus or treating the illness has been made. A major issue with the spread of Ebola Hemorrhagic Fever, the disease caused by the Ebola Virus, concerns the burial practices of the mourners in places where Ebola is found most often. Another level of concern, is the relatively high infection rate amongst monkeys, gorillas, and other simians, especially since Ebola-Reston, which currently only affects monkeys (and now reportedly pigs in the Philippines), is possibly transmitted through air-borne means. The fatality rate of this lethal virus has been reported at 25-90% and the morbidity rate is also very high, the virus often ending the victims life through external and internal bleeding.

Picture of Ebola from the WHO pdf on Ebola Viruses. Gorilla from Google Images.

The disease can remain in an incubation period from as little as two to twenty one days before symptoms begin to show. The initial symptoms include intense fever, headaches, muscle pain, sore throat, hiccups, and intense weakness, which are usually followed up by diarrhea, impairment of liver and kidney functions, rash, red eyes, vomiting, and both internal and external bleeding. The virus causes many of these symptoms by decreasing the white blood cell and platelet count in victims, as well as by inhibiting the production of certain enzymes in the liver. 

This video shows a 3d image of what an Ebola virus looks like.

Ebola Virus Animation




J Virol. 2002 Jul ;76 (13):6841-4 12050398

J Virol. 2003 Jul ;77 (14):7945-56 12829834

Lippincott, Williams, & Wilkins. Field's Virology. Wolters Kluwer, 2007.

Structure Of Key Ebola Protein Discovered
ScienceDaily (Jan. 13, 2009)

Although so little is known about how the proteins play a role in the pathogenicity of the Ebola virus, it is proposed that the virion glycoprotein (VP35), in its transmembrane form, allows it to enter into the cell, as well as to begin interacting with the endothelial cells. This directly attributes to the hemorrhagic symptoms of the disease caused by ebola.  After entrance into the cell itself, the secreted version of the virion glycoprotein inhibits the neutrophil activation of the cells, thus affecting the host's response to the infection. Both of these involve causing cytotoxic effects of human cells both inside the human body, as well as in a controlled laboratory environment. Though there have been a number of claims as to inhibitors of the ebola virus proteins, such as the CV-N found in blue-green algae, there is no information concerning the effect of removing these proteins to produce attenuated versions of the virus for use in vaccines.

Proteins & the Replication Cycle
As can be seen in the  diagram above, there are a number of proteins that are directly correspondent to different jobs needed in order for the virus to successfully infect and commandeer the cell to create more copies of itself.  In the first phases of viral infection of the ebola virus, the glycoprotein, or GP, comes in contact with the exterior of the cell.  The receptors on this external casing bind with the cell's endothelial membrane, which then creates a little vacuole to allow the virus inside.  The ebola virus glycoprotein play an extremely significant part in the research and development of its pathogenicity, as well as in researching an effective vaccine and will be discussed further below. After the glycoprotein has tricked the cell into allowing the virus inside, it shed's its outer casing and releases its nucleocapsid, which contains all of the RNA material needed to reproduce the virus. After the entry of the virus into the host cell, the cell's own polymerase comes and begins to make copies of the RNA.  The VP35 protein is used by the virus to interfere with the cell's inclusion information, making it believe that the virus' RNA is its own, halting regular cell production. The L protein then begins the cycle of replication, by carrying out the binding, polymerasing activities, and all other patterns linked to RNA transcription. All of this occurs without the body's defense cells being able to recognize what is going on. The nucleoprotein (NP) and VP30 aid in triggering the activation of the replication of the virus. The VP40 and VP24, VP40 being the "president" & VP24 being the VP, proteins act as a sort of mastermind in the assembly-line of new viruses, as well as the budding and detachment from the cell that occurs when each new ebola virus is released. VP40 is the most plentious protein within the ebola virion, and is a critical player in the replication cycle, namely the budding process. This is due to its initial and subsequent forcing of the plasma membrane envelopment of the NC. (Note the VP40 portion of the picture below).

Glycoproteins & a Step Toward Vaccination
Glycoproteins are the most studied protein of the filovirus proteins because of how it gains entry into the cell, pathogenicity, antigenicity, and its possible roll in vaccine development. As noted before, the structural glycoproteins, or SGP, could be largely responsible for the rate of progression in the disease, since large quantities of SGP have been found in the blood of ebola victims.  In a recent finding by
Gaya Amarasinghe, the VP35 glycoprotein's structure was uncovered using x-ray crystallography and nucleic magnetic resonance spectroscopy.  This is extremely important in the fight against ebola, since the VP35 glycoprotein is the protein responsible for the immune system's inability to stop the infection.  In short, the VP35 prevents the body's antibodies from bonding to the virus, which would eventually lead to the body winning out over the virus.  With part of the structure of VP35 mapped out, it is entirely possible that a drug could bind with it to render the glycoprotein basically useless.  Without useable VP35 glycoproteins, the ebola virus would essentially become dead in the water, since it would not be able to replicate.