Clinical features and pathobiology of Ebolavirus infection.

There has clearly been a deluge of international press coverage of the recent outbreak of Ebolavirus in Africa and is partly related to the "fear factor" that comes across when one is confronted with the fact that once infected, not only is the speed of death in a majority of cases rapid but also the images of the cause of death such as bleeding from various orifices gruesome and frightening. The fact that it leads to infection and death of health care providers (10% during the current epidemic) and the visualization of protective gear worn by these individuals to contain such infection adds to this "fear factor". Finally, there is a clear perceived notion that such an agent can be utilized as a bioterrorism agent that adds to the apprehension. Thus, in efforts to gain an objective view of the growing threat Ebolavirus poses to the general public, it is important to provide some basic understanding for the lethality of Ebolavirus infection that is highlighted in Fig. 1. This virus infection first appears to disable the immune system (the very system needed to fight the infection) and subsequently disables the vascular system that leads to blood leakage (hemorrhage), hypotension, drop in blood pressure, followed by shock and death. The virus appears to sequentially infect dendritic cells disabling the interferon system (one of the major host anti-viral immune systems) then macrophages (that trigger the formation of blood clots, release of inflammatory proteins and nitric oxide damaging the lining of blood vessels leading to blood leakage) and finally endothelial cells that contribute to blood leakage. The virus also affects organs such as the liver (that dysregulates the formation of coagulation proteins), the adrenal gland (that destroys the ability of the patient to synthesize steroids and leads to circulation failure and disabling of regulators of blood pressure) and the gastro-intestinal tract (leading to diarrhea). The ability of the virus to disable such major mechanisms in the body facilitates the ability of the virus to replicate in an uncontrolled fashion leading to the rapidity by which the virus can cause lethality. Various laboratories have been working on defining such mechanisms utilizing in vitro culture systems, a variety of animal models including inbred strains of normal and select gene knock out mice, guinea pigs and nonhuman primates that have led to a better understanding of the potential mechanisms involved. There have also been some major advances made in the identification of therapies from the very simple (major supportive type of therapy), to the identification of a number of highly effective chemotherapeutic agents, a variety of highly effective preventive (demonstrating 100% effectiveness in nonhuman primate models) recombinant formulations (adenovirus based, VSV-based, rabies virus based), therapeutic candidate vaccines (cocktail of monoclonal antibodies such as ZMAPP) and alternate approaches (RNAi-based such as TKM-Ebola and antisense based such as AVI-7537) that show great promise and at an unprecedented rate of discovery that speaks well for the scientific research community at large.