Nzegge-Ekane 1 Shiren Nzegge-Ekane Concordia University, MPH program Biological and Molecular Characteristics of Ebola Virus 11/21/14 Nzegge-Ekane 2 The Ebola virus comes from the viral family Filioviridae, also known as Filovirus. Like all virus, the Filovirus will attack the host’s immune system and utilize its machinery. The virus is RNA-dependent. While in the host’s cells, the virus will replicate, lyse the cells, and release the newly created virus (virions). These virions will continue attacking other cells. Their presence and action can cause an inflammatory response as well as brief burst of clotting activity. This mechanism will cause organ failure since there is not enough blood-oxygen to be delivered to the organs. Profuse bleeding occur both internally and externally (nose, eyes, ears, mouth, and skin), which is as a result of impaired clotting factors. The outbreak this year has consumed a lot of lives (thousands), making it more significant than that of 1976 (hundreds). This has puzzled public health officials. Only the biological and molecular aspects of the virus can best explain why this new strain of the Ebola virus is so severe. In public health, assessment is the first step to combat any outbreak. This is simply identifying the disease and its causative agent. With the help of electron microscope, this task can be accomplished. Ebola virus (Zaire virus), under the electron microscope looks like a worm-like or spiral structure. However, going deeper into the genomics of the virus requires not just electron microscope but techniques that will enable the extraction of the nucleic acids and other important protein which will explain why this new strain is so unique as a killing machine. Ebola virus is a single stranded RNA-depended virus. This means that while in the cell, it undergoes reverse transcriptase as a step to initiate replication. With the help of antigen capture and IgM and IgG Immunoassay (ELISA), determination of the viral antigen in the serum of an infected individual can be screened (Towner et al., 2008). To study the virus in depth, first thing to do is to isolate the virus and perform reverse transcriptase, real-time PCR, genome sequencing, and random-primes pyro sequencing which is Nzegge-Ekane 3 very effective and specific in determining the genome of the virus. (Towner et al., 2008) The results of these techniques can provide a clue why the new virus is fatal compared to the previous ones. The Ebola virus has a negative strand RNA virus that is unique in encapsidating the RNA genome with a viral coded nucleoprotein, there by forming a ribonucleoprotein (RNP). The RNP is a protein structure that prevents attacks from the nuclease. The nucleoprotein can polymerized to envelope the entire genome hence protecting it from digestion by the ribonuclease. The most interesting part is the fact that the virus has multiple binding surfaces which as Cleveland (2011) noted, “Once the [surface] is changed, given the constraints operating on it, the mutation can be compensated with an additional mutation of a corresponding residue elsewhere in the protein that are closer when folded,” (Cleveland et al., 2011). Since 1976, constant change (mutation) has altered the surface proteins of the virus. This is why it has been very difficult to find the cure and vaccines of the disease. The specific receptor found in “soup” of the cure always fails during the trial because of the constant change or fold of the surface protein with others nearby. The cells that are mostly affected are parenchymal cells, macrophages, dendrites, and endothelial cells found in most organs in the body. Other cells affected are hepatocytes, adrenal cortical cells, fibroblast, to name the few. This always causes the body to respond through inflammation. This is exactly what happened to the outburst and shutdown of the clotting factors. Cell surfaces of infected macrophage will trigger extrinsic coagulation pathway which can be seen by the increase D-dimer levels from laboratory report of an infected individual (Bray, 2014). Acute phase of the disease will show activity of multiple cytokines through analysis of the molecular Ribonucleic acid (mRNA). The activated cytokines along with chemokines and other proinflammatory mediators will cause shock and defect in the vasculature. Also, there is Nzegge-Ekane 4 circulation of soluble glycoprotein which prevents effective immune response of the host’s immune system (Peters and Peters, 1999). This is because dendrites cells which are responsible for initiation of adaptive immune response have been impaired. As the host becomes immunosuppressive, necrosis of the spleen and lymphatic system as well as other tissues kicks in. Laboratory report of white blood cell count will be very low. Every success in the intervention and prevention of Ebola disease by public health officials is primarily on the assessment. Assessment comprises of identification of the disease and its causative agents. Also, knowledge about the biological and molecular characteristics of the virus is of great significance to health care officials. The Ebola outbreak of 2014 has showed that it is more different than those from previous years which is due to its severity, evolution, and genetic aspects. It has been 38 years since the first Ebola outbreak, giving it enough time for mutation to occur. The virus has really changed. By assessing the genome of the new Ebola virus (Zaire virus) and comparing it to that of the old, one will see a lot of difference in the genomic. This has caused difficulties in getting effective treatment plan as well as delay in the production of the vaccines hence causing more death Nzegge-Ekane 5 Reference: Cleveland B., Davies, and McClure. 2011. A Bioinformatics Approach to the Structure, Function, and Evolution of the Nucleoprotein of the Order Mononegavirales Peters J. and Peters. 1999. An Introduction to Ebola: The Virus and the Disease Bray. 2014. Epidemiology, pathogenesis, and clinical manifestations of Ebola and Marburg virus disease Towner S., Sealy, Khristova, Albarino, Conlan, Reeder, Quan, Lipkin, Downing, Tappero, Okware, Lutwama, Bakamutumaho, and Nichol. 2008. Newly Discovered Ebola Virus Associated with Hemorrhagic Fever Outbreak in Uganda