Description

Genevieve Bruen May 6, 2019 Ebola Virus Review In the 2014-16 outbreak of Zaire ebolavirus, referred to as Ebola virus, in West Africa there were 28,652 cases of infection and approximately 11,325 deaths (“2014-2016 Ebola Outbreak in West Africa”). Since August 2018, the current Ebola virus outbreak in the Democratic Republic of Congo (DRC) has caused confirmed infections in 1,488 people, resulting in 1,029 deaths as of this writing (Ebola situation reports: Democratic Republic of the Congo”). The number of Ebola virus infections and deaths in the DRC continues to rise rapidly. Ebolaviruses are an aggressive genus of viruses that belong to the family Filoviridae. There are four species of Ebolavirus that have the ability to cause disease in humans including: Ebola virus (Zaire ebolavirus), Bundibugyo ebolavirus, and Sudan ebolavirus (Malvy et al. 936). Taï Forest ebolavirus, a fourth species of ebolavirus, has only been responsible for one human infection (“Ebola Virus Disease Distribution Map”). Ebola virus has a single strand of negative sense RNA (Malvy et al. 936). Negative sense means that in order for the virus to be replicated, it must be converted into the proper form of RNA first (Cowan, Smith and Lusk 130). Ebola virus can cause severe Ebola Virus Disease (EVD) that can be fatal. Total case fatality for Ebola virus (Zaire ebolavirus) has been 80% (Malvy et al. 936). It is important to learn about Ebola’s structure, how it causes disease, the symptoms it causes, and how the virus is spread so that we can develop better ways to prevent it. In order to understand the way Ebola virus causes disease and how to prevent it, researchers study the viral structure and how the structure influences the virus’s ability to enter the cell and cause disease. Ebola contains seven proteins referred to as Viral Proteins (VP), a single strand of RNA, viral glycoproteins, and an envelope membrane (Goodsell 1). The matrix protein of the Ebola is made up VP 40 which provides structural integrity to the Ebola virion (Falasca et al. 1251). The matrix also enables replicated virions to be released from the host cell by a process called budding (Rivera and Messaoudi 186). “The matrix protein of ebola is particularly unusual because it adopts entirely different structures for its different jobs: as a hexamer in the virion structure, as an octamer that binds to RNA and regulates viral transcription, and as a dimer involved in transport of the protein” (Goodsell 2). Ebola’s matrix protein takes on different shapes to serve different functions during the various stages of the infection (Gnida).The nucleocapsid is formed by VP35, VP30, and VP25 (Goodsell 1). The nucleocapsid wraps around the RNA and protects it (Goodsell 2). Its structure looks wavy because of its filamentous structure and its viral proteins interactions are not rigid (Goodsell 2). The L protein in the Ebola virion creates new copies of the RNA when the virus is replicated inside of the host cell. The envelope membrane is “stolen” from host cells (Goodsell 1). The entrance of Ebola virus into the host cell involves the viral glycoproteins, the receptors on host cells that are tropisms for the virus, and certain mechanisms involved. Entry into a host cell is intregal to the virus’s ability cause disease, because the Ebola virus must enter into cells and use their machinery to replicate and cause disease. The viral glycoprotein of Ebola protrudes from the surface of the virus and is covered with carbohydrate to conceal it from the immune system (Goodsell 1). The glycoprotein binds receptors on the tropism cells of the host, which are the target tissues. According to Dr. Goodsell, the binding of the glycoprotein to the receptor causes a shape change that drags the Ebola virus close enough to the host cell for the membranes to fuse together, allowing the virus to enter into the cell (1). Other methods used by Ebola virus to enter into target cells after binding receptors are macropinocytosis and receptor-mediated endocytosis (Falasca et al. 1251). Macropinocytosis involves the cell “drinking-in” extracellular fluid and the nearby molecule, in this case Ebola virus. Receptor-mediated endocytosis occurs when the host cell engulfs the Ebola virus. All the receptors that are involved in Ebola virus internalization are not known, but two of them have been identified. Niemann-Pick C1 (NPC1), an endosomal protein on host cells, has been shown to be an entry receptor that primes the virus glycoprotein for fusion of membranes and binds to ebolavirus (Wang et al. 258). The T-cell immunoglobulin and mucin domain 1, TIM-1, on host cells is a binding site for Ebola virus and is found on many human cells (Kondratowicz et al. 8426). There are a wide range of target cells, known as tropisms, that the Ebola virus can infect. The target cells it attacks lend some insight into the damage that Ebola inflicts. Ebola has shown the ability to infect monocytes, macrophages, dendritic cell,