The Relationship Between Ebola Virus and Host Factors

By: Amanda He (currently being edited)

Introduction to Ebolavirus

Ebolaviruses (EBOV) are enveloped viruses that belong to the Filoviridae family. EBOV has received a significant amount of international attention because it causes severe hemorrhagic fevers in humans with a fatality rate of approximately 60% [1]. A minority of cases with infection results in flu-like symptoms with the addition of mild blood coagulopathy, blood loss, and increase in white blood cells, but these patients have a full recovery. The majority of cases develop severe illness with excessive hemorrhaging and blood clotting, which results in shock and death. However, it is important to note that a major factor of the fatality rate of Ebolavirus disease is the access to proper healthcare. EBOV is extremely infectious and can be transmitted through exposure to bodily fluids such as feces, saliva, urine, vomit, and semen from an infected individual and can enter the body through broken skin or unprotected mucous membrane. For a healthcare worker who may be interacting with a number of different patients, it is important to wear appropriate protective equipment and practice appropriate infection control and sterilization measures [2]. Potentially infected individuals must be isolated from other patients to prevent further outbreaks. Although an individual may be infected, the symptoms are not automatic as the virus has an incubation period ranging from 2 to 21 days [3]. The average incubation period is 7-10 days. Through isolation of a potentially infected individual, it can prevent the spread to others.

Several studies have characterized EBOV infection to disable the immune system and the vascular system. The disabling of the vascular system is what leads to the symptoms such as hemorrhage, hypotension, and blood pressure drop [Ansari]. Autopsy of EBOV infected patients found the viruses located primarily in the endothelial cells, mononuclear phagocytic cells, and several fibroblasts and hepatic sinusoids [3]. As a result, it is likely that the initial infection of EBOV targets macrophages and monocytes [4]. The infection of macrophages and monocytes leads to increased synthesis of tumor necrosis factor-α (TNF-α), which induces fever and lymphoid cell apoptosis [3]. Additionally, infection of macrophages and monocytes can induce the release of various pro-inflammatory proteins.

As of 2014, there are no approved therapeutic strategies to treat infection. As a result, there has been a significant emphasis on studying the host factors EBOV recruits [5]. Host factors are traits found in an individual that could have an effect on their susceptibility to disease. In recent studies, certain host factors such as cathepsin B, heat shock 70 kDa protein 5, and STAT1 have been identified to play a role in EBOV infection. Further investigation of host factors can help grasp a better understanding about EBOV and potentially lead to a treatment.

Ebola Genome and Replication Cycle

Figure 2: The negative-strand RNA genome of Ebolavirus.
Image source: http://viralzone.expasy.org/all_by_species/207.html [6]

EBOV has a filamentous shaped virus with a lipid envelope, lipid bilayer coat, and genome. The lipid bilayer coats serves as a mechanism to protect the genome and assists with entry into the host cell [6]. The genome of EBOV consists of single stranded, nonsegmented, negative-sense RNA virus with approximately 19,000 bases [7]. The EBOV genome encodes for seven proteins: glycoprotein (GP), matrix protein viral protein 40 (VP40), nucleoprotein (NP), viral protein 24 (VP24), viral protein 30 (VP30), viral protein 35 (VP35), and large protein, an enzyme subunit (L) [1].

Each of these proteins play a significant role in EBOV infection. GP is found on the viral envelope and plays a role in viral attachment and entry into the host cell [7]. VP40 is found in the viral lipid coat and plays a role in virus structure and stability [1]. Researchers found that with the expression of only one EBOV protein, VP40, the virus is still able to form virus like particles in human cells. All the remaining proteins are used to compose the nucleocapsid. The nucleocapsid is the capsid surrounding the RNA, which plays an important role in viral transcription and replication.

Cathepsin B and Ebolavirus Entry

HSPA5 and VP40

An endoplasmic reticulum (ER) chaperone called heat shock 70 kDa protein 5 (HSPA5) has been identified as a EBOV-associated host factor [Spurgers, et al 2010]. HSPA5 is a highly conserved ER protein that assists with protein folding and assembly. It has additional roles in regulation of ER stress responses. However, various viruses are able to utilize HSPA5 for their own purposes such as assistance in development of mature viral envelope proteins and viral entry [5]. It is likely that HSPA5 may be utilized by EBOV assist in infection.

[Image: Reid Fig 1.jpg]