Overview of Ebola Virus Disease:
The Ebola virus causes an acute, serious illness which is often fatal if untreated. The latest outbreak that occurred in West Africa, (first cases notified in March 2014) is the largest and most complex Ebola outbreak since the Ebola virus was first discovered in 1976. The virus enters the human population through human-to-human transmission after being conveyed to humans by wild animals.
Ebola Virus Morphology:
- Ebola Virus are approximately 80 nm in diameter, 970 nm long.
- They are cylindrical and contain viral envelope, matrix, and nucleocapsid components.
- Seven open reading frames of the 19 kb Ebola virus genome encode structural proteins like the virion envelope glycoprotein (GP), nucleoprotein (NP), and matrix proteins VP24 and VP40; nonstructural proteins like VP30 and VP35; and the viral polymerase.
- They have a virally encoded glycoprotein projecting as 7-10 nm long spikes from its lipid bilayer surface.
- The glycoprotein is the sole resident of the Ebolavirus surface and is responsible for attaching to and entering new host cells.
Ebola Virus Replication Cycle:
Attachment and Host Cell Entry
Virus attaches to host receptors through glycoprotein which is endocytosed into vesicles in the host cell. Host DC-SIGN [Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) also known as CD209 (Cluster of Differentiation 209)] and DC-SIGN play a role in virion attachment.
Viral Penetration and Endocytosis
Through clathrin-mediated endocytosis or macropinocytosis, the virion penetrates early endosomes. During macropinocytosis, the virus uses glycoproteins to adhere to the surface of the host’s plasma membrane, causing ruffled sections of the membrane to protrude from the cell and produce invaginations.
Clathrin-mediated endocytosis is the other means by which Ebolavirus enters the host cell. Glycoproteins present on envelope of the virus are attached to the cell surface, and the NP-C1[(Niemann-Pick disease, type C1), a membrane protein mediates intracellular cholesterol trafficking in mammals] cholesterol transporter facilitates the fusion of the virus with endosomes and allows the virus to escape into the cytoplasm. The ebolavirus cannot exit the vesicle to multiply and infect additional cells in the absence of the NPC1 cholesterol transporter. The nucleocapsid is released into the cytoplasm after the viral membrane fuses with the vesicle membrane to enter the cell. Either low pH or NPC1 binding causes the viral membrane to fuse with the vesicle membrane.
Transcription & Protein Synthesis
The RNA genome is converted into seven monocistronic mRNAs during transcription. The polymerase complex binds to a single binding site in the genome’s leader region to start the transcription process.
The various genes are then consecutively transcribed in their 3′ to 5′ order as the complex moves along the RNA template. Encapsidated, negative-sense genomic ssRNA serves as a template for the creation (3′–5′) of polyadenylated, monocistronic mRNAs, which are then translated into distinct viral proteins by the host cell’s ribosomes, tRNA molecules, etc.
Genome Replication
Translation gives way to replication as viral protein levels increase. A complementary +ssRNA is created using the negative-sense genomic RNA as a template; this is subsequently utilized as a template for the creation of additional genomic (-)ssRNA, which is quickly encapsidated. When there is sufficient nucleoprotein to encapsidate neosynthetized genomes and antigenomes, replication most likely begins.
Assembly and Budding
The ribonucleocapsid interacts with the matrix protein, and buds via the host ESCRT (endosomal sorting complex required for transport) complexes from the plasma membrane, releasing the virion
Pathogenesis of Ebola Virus:
- Ebola virus is highly effective at replicating in a variety of cells, including monocytes, macrophages, dendritic cells, liver cells, fibroblasts, and adrenal gland cells.
- High quantities of inflammatory chemical signals are released during viral replication, which results in a septic state.
- The primary targets of infection are liver cells, endothelial cells (the cells that line the inside of blood arteries), and other immune cell types, including macrophages, monocytes, and dendritic cells.
- After being infected, the virus is transported by immune cells to adjacent lymph nodes, where it reproduces further. From there, it can enter the circulation and lymphatic system and spread throughout the body.
- The virus first infects macrophages, and this infection causes programmed cell death. The concentration of lymphocytes in the blood is abnormally low because other forms of white blood cells, like lymphocytes, also experience programmed cell death. This adds to the compromised immune response observed in Ebola virus-infected individuals.
- Within three days of being exposed to the virus, endothelial cells can become infected. Ebola virus glycoproteins are responsible for the breakdown of endothelial cells that results in blood vessel damage. This damage is brought on by the production of Ebola virus glycoprotein, which damages the liver and prevents normal clotting by reducing the availability of certain integrins that are necessary for cell attachment to the intercellular structure.
- Due to the loss of blood volume, the extensive bleeding that afflicted individuals experience results in shock and edema.
- A secreted glycoprotein called small soluble glycoprotein (sGP or GP) is created upon infection.
- The host immune system and the protein synthesis of infected cells are overwhelmed by Ebolavirus replication.
- By interfering with neutrophil signaling, the sGP form allows the virus to avoid the immune system by blocking the initial stages of neutrophil activation.
-  In addition to experimentally infected non-human primates, the presence of viral particles and the cell damage caused by viruses bursting out of the cell result in the production of chemical signals (such as TNF-α, IL-6, and IL-8), which are molecular signals for fever and inflammation.