Ebola virus disease (EVD) is a rare but severe illness that can often be fatal in humans. It is caused by the Ebola virus, which belongs to the Orthoebolavirus genus within the Filoviridae family. First identified in 1976 in areas near the Ebola River in the Democratic Republic of Congo and in Sudan, this disease represents a public health concern, particularly in parts of Africa where outbreaks have occurred regularly.
Understanding the Ebola Virus Particle
When people refer to an “Ebola cell,” they are actually describing the Ebola virus particle, also known as a virion. The Ebola virus is not a living cellular organism but rather an infectious agent that relies on host cells to replicate. These virions exhibit a distinct filamentous or thread-like shape, though they can also appear U-shaped, in the shape of a “6,” or even circular.
An Ebola virus particle includes a viral envelope, a lipid membrane derived from the host cell during budding. This envelope is studded with virally encoded glycoprotein (GP) spikes, which are important for attaching to and entering new host cells. Beneath the viral envelope lies a layer of matrix proteins, primarily VP40 and VP24, which provide structural support and help shape the virus.
At the core of the virus is its genetic material, a single-stranded negative-sense RNA genome that contains seven genes. This RNA genome is tightly packaged within a helical nucleocapsid, formed by nucleoprotein (NP) and associated with other viral proteins, including the RNA polymerase (L protein). The nucleocapsid protects the viral RNA and serves as the template for replication and transcription once inside a host cell.
How Ebola Invades and Replicates in Cells
The Ebola virus initiates infection by targeting specific human cell types, including macrophages, dendritic cells, and liver cells (hepatocytes). The virus uses its glycoprotein (GP) to bind to receptors on the surface of host cells. Following attachment, the virus enters the host cell primarily through a process called macropinocytosis, where the cell’s plasma membrane engulfs the virion into a vesicle.
Once inside the endosome, the viral glycoprotein undergoes proteolytic cleavage by host proteases, which removes parts of the glycoprotein and exposes its receptor-binding domain. This processed glycoprotein then interacts with an intracellular receptor, Niemann-Pick C1 (NPC1). This interaction, along with a low-pH environment within the endosome, triggers the fusion of the viral membrane with the endosomal membrane, releasing the viral nucleocapsid into the host cell’s cytoplasm.
Upon release into the cytoplasm, the viral RNA genome serves as a template. The viral RNA-dependent RNA polymerase (L protein) transcribes the negative-sense RNA genome into messenger RNAs (mRNAs), which are then translated into viral proteins. As viral protein levels increase, new copies of the viral genome are synthesized, and the replication process begins. These newly synthesized genomes and viral proteins then assemble into new virus particles, which bud from the host cell’s plasma membrane, acquiring their lipid envelope, ready to infect other cells.
The Impact of Ebola on Host Cells and the Body
Ebola virus infection causes direct damage to infected cells, leading to cytopathic effects such as cell death and disruption of normal cellular functions. The virus preferentially targets immune cells like macrophages and dendritic cells early in infection, which are important for initiating an effective immune response. This early infection of immune cells allows the virus to rapidly spread throughout the body and evade the host’s defenses.
A major consequence of Ebola infection is an uncontrolled inflammatory reaction, often referred to as a “cytokine storm.” This involves the release of pro-inflammatory cytokines and chemokines by immune cells. While the virus itself may not productively infect lymphocytes, the cytokine storm can lead to their activation and subsequent death, contributing to lymphopenia (a decrease in lymphocyte count). The viral proteins VP24 and VP35 also interfere with the host’s antiviral defenses, inhibiting interferon signaling and further compromising the immune response.
The widespread infection and dysregulated immune response lead to systemic effects. The virus attacks various organ systems, including the liver, kidneys, spleen, and blood vessels. Damage to the liver can impair the synthesis of blood clotting proteins, contributing to hemorrhagic symptoms. Infection of endothelial cells lining blood vessels causes them to leak fluid into surrounding tissues, leading to dehydration within the blood vessels and potentially hypovolemic shock. The accumulation of cellular damage and immune dysregulation progresses to symptoms like fever, fatigue, vomiting, diarrhea, and in severe cases, internal and external bleeding, culminating in multi-organ dysfunction and a high fatality rate.