Ebola Virus Disease (EVD) is a rare but severe illness in humans and non-human primates caused by viruses in the genus Ebolavirus, which belongs to the Filoviridae family. Ebola is not a cell but a virus particle, or virion, which is an acellular infectious agent. The virion is composed of genetic material enclosed within a protein shell and a lipid envelope, requiring a host cell to replicate and cause the disease. The process by which this particle takes over a living cell and leads to a systemic, often fatal, illness is a complex biological mechanism.
Structure of the Ebola Virion
The Ebola virus particle is characterized by its distinctive filamentous, thread-like shape, which is the defining feature of the Filoviridae family. While typically long and tube-like, the virion can also appear coiled, branched, or in shapes resembling a “6” or a shepherd’s crook. These particles are approximately 80 nanometers in diameter but can reach lengths up to 14,000 nanometers.
The virion structure contains a core with the genetic material, a single-stranded, negative-sense RNA genome. This RNA is encased in a helical nucleocapsid, formed by the nucleoprotein (NP) and other viral proteins like VP35 and VP24. Surrounding the nucleocapsid is a matrix layer, composed primarily of viral protein 40 (VP40), which provides structural stability and determines the particle’s filamentous shape.
The complex is enclosed by a lipid envelope derived from the host cell membrane during budding. Spikes of the viral glycoprotein (GP) stud this outer envelope. The GP is the component responsible for recognizing and attaching to the host cell, initiating infection.
Cellular Entry and Replication Cycle
The infection process begins when the Ebola virion encounters a susceptible host cell, primarily targeting immune cells such as monocytes, macrophages, and dendritic cells. The viral glycoprotein (GP) interacts with attachment factors on the host cell surface, facilitating the uptake of the entire virus particle. This internalization occurs through macropinocytosis, where the cell engulfs the virion in a large vesicle.
Once inside the host cell, the virus-containing vesicle, or endosome, is trafficked toward the cell’s interior, becoming progressively more acidic. Within this acidic environment, host cell enzymes, specifically cathepsins, cleave the viral glycoprotein. This cleavage exposes the receptor-binding domain of the GP.
The newly exposed domain then binds to Niemann-Pick C1 (NPC1), a cholesterol transporter protein on the endosomal membrane. NPC1 acts as the required fusion receptor, facilitating the fusion of the viral envelope with the endosomal membrane. This fusion event releases the viral nucleocapsid and its RNA genome into the host cell’s cytoplasm, marking the beginning of replication.
Inside the cytoplasm, the viral RNA-dependent RNA polymerase complex transcribes the negative-sense genome into messenger RNA (mRNA) to create viral proteins. Full-length positive-sense antigenomes are also created, which serve as templates for synthesizing new negative-sense viral genomes. These newly synthesized structural proteins and genomic material self-assemble near the inner surface of the host cell membrane. New virions are then released from the infected cell through budding, acquiring their lipid envelope and surface GP spikes from the host cell membrane as they exit.
Systemic Pathogenesis and Disease Progression
The infection of monocytes, macrophages, and dendritic cells is significant because these cells are central to the innate immune response and widely distributed throughout the body. The virus rapidly exploits these cells to disseminate throughout the host, spreading to vital organs such as the liver, spleen, and adrenal glands. This widespread infection leads to high viral loads, which is strongly correlated with a fatal outcome.
A defining characteristic of Ebola virus pathogenesis is its ability to subvert the host’s immune system by blocking the production of type I interferons (IFNs). Viral proteins, such as VP35, interfere with the signaling pathways necessary to produce these antiviral molecules, effectively silencing the immune response. This suppression allows the virus to replicate unchecked during the initial days of infection.
As the infection progresses, the widespread death of infected cells, coupled with a massive, dysregulated inflammatory response known as a “cytokine storm,” causes significant damage. The virus also infects endothelial cells lining the blood vessels, leading to increased vascular permeability and vasodilatation. The resulting blood vessel damage and leakage, along with coagulation abnormalities, contribute to hemorrhagic symptoms and cause shock from fluid loss.
The systemic damage results in multi-organ failure, particularly affecting the liver and kidneys. Destruction of liver cells impairs the body’s ability to produce coagulation factors, exacerbating bleeding issues. This combination of immune suppression, widespread viral replication, vascular collapse, and organ failure defines the severe progression of Ebola Virus Disease.
Transmission Routes and Containment
Ebola virus is introduced into the human population through a spillover event, typically involving direct contact with the blood, organs, or other bodily fluids of an infected animal, such as fruit bats or non-human primates. Once in the human population, the virus spreads through direct contact with the bodily fluids of a person who is sick or has died from EVD. Infectious fluids include:
- Blood
- Vomit
- Diarrhea
- Urine
- Saliva
- Semen
Transmission requires the virus to enter the body through broken skin or mucous membranes. The virus can also be transmitted indirectly through contact with contaminated objects or surfaces, such as needles, clothing, or bedding. Ebola is not considered an airborne disease, as its spread does not occur through the inhalation of small, dried aerosol droplets.
Safe burial practices are a crucial component of containment, as the bodies of deceased individuals remain highly infectious. Infection control measures in healthcare settings, including the use of personal protective equipment (PPE), are paramount to preventing nosocomial transmission. For survivors, the virus can persist in protected sites like the testes or eyes, and sexual transmission from male survivors has been documented, necessitating safe sex practices after recovery.