Ebola virus disease (EVD) is a severe and often fatal illness caused by the Ebola virus, a member of the Filoviridae family. This family of viruses is characterized by its filamentous shape and single-stranded, negative-sense RNA genome. First identified in 1976 following outbreaks in present-day South Sudan and the Democratic Republic of the Congo, Ebola virus has since caused sporadic outbreaks, primarily in Africa.
How Ebola Enters Host Cells
Ebola virus initiates infection by first attaching to the surface of a host cell. This attachment involves the viral glycoprotein (GP) interacting with various molecules on the host cell surface. The virus primarily targets immune cells, such as macrophages and dendritic cells, and can also infect liver cells, leading to systemic spread throughout the body.
Following attachment, the virus enters the cell predominantly through a process called macropinocytosis, where the cell’s plasma membrane actively engulfs the viral particle. Once inside the cell, the virus is contained within an endosomal compartment, which then traffics through a series of early and late endosomes.
Within these acidic endosomal compartments, the viral glycoprotein undergoes proteolytic cleavage by host enzymes, which exposes a binding site. This allows the virus to interact with an intracellular receptor, Niemann-Pick C1 (NPC1), located on the endosomal membrane. This interaction triggers the fusion of the viral membrane with the endosomal membrane, releasing the viral genetic material, the ribonucleoprotein (RNP) complex, into the host cell’s cytoplasm.
Replication and Protein Synthesis
Once the viral ribonucleoprotein (RNP) complex is released into the host cell’s cytoplasm, the Ebola virus begins to replicate its genetic material and produce viral proteins. Its RNA genome is encapsulated by a nucleoprotein (NP) and associated with viral proteins, including the RNA-dependent RNA polymerase (RdRp) and VP35. This complex serves as the template for both transcription and replication.
The viral RdRp first transcribes the negative-sense genomic RNA into messenger RNAs (mRNAs). These mRNAs are then translated by the host cell’s ribosomes into the various viral proteins needed for new viral particles. Simultaneously, the RdRp also replicates the viral genome by first synthesizing a full-length positive-sense RNA antigenome, which then serves as a template to produce new negative-sense RNA genomes.
These processes occur within specialized compartments in the host cell cytoplasm. These structures are not membrane-bound but represent organized sites where viral components are concentrated. The nucleoprotein (NP) plays a central role in encapsidating the newly synthesized RNA, forming new RNP complexes for the assembly of progeny virions.
Assembly and Release of New Virions
After the replication and protein synthesis phases, the newly manufactured viral components begin to assemble into new virus particles. The nucleocapsids, which are complexes of the viral genome and associated proteins, accumulate within the host cell’s cytoplasm and are then transported toward the plasma membrane. The viral matrix protein VP40 is a key driver of this assembly.
The viral glycoprotein (GP) also migrates to the plasma membrane. At the budding sites on the cell membrane, the nucleocapsids, along with other viral proteins like VP40 and GP, gather. The new virion then buds off from the host cell, acquiring a lipid envelope derived from the host cell’s plasma membrane.
This release process leads to damage and death of the infected host cell, contributing to the pathology observed in Ebola virus disease.
Transmission Between Hosts
The life cycle of the Ebola virus extends beyond a single host cell to include its transmission between individuals and populations. Ebola virus is primarily transmitted through direct contact with the blood, secretions, organs, or other bodily fluids of infected people, whether they are alive or have died. This includes fluids such as vomit, feces, urine, breast milk, saliva, and semen. Even contaminated surfaces and materials can facilitate indirect transmission.
Transmission from a person with Ebola disease occurs when they begin to show symptoms, as the virus is not considered contagious before symptom onset. The virus can persist in certain bodily fluids, such as semen, for months after clinical recovery, posing a risk of sexual transmission. Burial ceremonies involving direct contact with the body of a person who died from Ebola disease have also been identified as a source of transmission.
Fruit bats are considered the natural reservoir for Ebola virus. Spillover events, where the virus transmits from animals to humans, can occur through contact with infected animals or their bodily fluids, such as through hunting or consumption of bushmeat. Once a spillover event occurs, the virus can then spread rapidly through human-to-human contact, leading to outbreaks.