Rabies is a severe viral disease that affects the nervous system, posing a significant global health threat. Understanding how this virus operates at a microscopic level, specifically how it interacts with and manipulates host cells, is important for comprehending its devastating effects. The term “rabies cell” refers to the virus and its intricate ways of invading, replicating within, and altering infected cells. This cellular perspective reveals the mechanisms behind the disease’s progression and its impact on the body.
The Rabies Virus
The rabies virus, a member of the Lyssavirus genus within the Rhabdoviridae family, exhibits a distinct bullet-shaped morphology. This viral particle, known as a virion, is enveloped, possessing an outer lipid membrane.
Embedded within this outer envelope are numerous glycoprotein (G protein) spikes, important for the virus’s interaction with host cells. Beneath the envelope lies the matrix protein (M protein), forming a layer that provides structural integrity. The innermost core consists of a helical ribonucleocapsid (RNP), which houses the virus’s genetic material: a single-stranded, negative-sense RNA genome. This RNA genome is associated with three other proteins: the nucleoprotein (N protein), phosphoprotein (P protein), and the large polymerase protein (L protein). The N protein encapsulates the RNA, while the P and L proteins are involved in viral gene expression and replication.
Cellular Invasion and Replication
The process of rabies virus infection begins when the viral glycoprotein (G protein) on the virion’s surface binds to specific receptors on the host cell membrane. Key entry points include the nicotinic acetylcholine receptor, abundant at neuromuscular junctions.
Following attachment, the virus enters the host cell through endocytosis, where the cell membrane engulfs the virion. Once inside, the acidic environment triggers changes in the G protein, leading to the fusion of the viral envelope with the endosomal membrane. This releases the viral ribonucleocapsid (RNP) into the host cell’s cytoplasm.
Within the cytoplasm, the viral L protein begins transcribing the negative-sense genomic RNA into messenger RNAs (mRNAs). These mRNAs are then translated by the host cell’s ribosomes to produce the five viral proteins (N, P, M, G, L). The L protein also initiates the replication of the viral genome. New viral components self-assemble, forming progeny RNPs. These RNPs then migrate to the cell membrane, where the M protein helps in the budding process, forming new virions that acquire their lipid envelope and G proteins from the host cell membrane.
Neural Pathogenesis
After local replication, typically in muscle cells at the site of exposure, the rabies virus demonstrates a strong affinity for the nervous system, known as neurotropism. The virus then enters peripheral nerve endings and utilizes the cell’s internal transport machinery to move towards the central nervous system (CNS). This movement occurs via retrograde axonal transport, where the virus travels backward along the axons, towards the neuron’s cell body.
Upon reaching the neuron’s cell body, the virus replicates extensively within the neurons of the spinal cord and brain. This widespread infection of neural cells leads to neuronal dysfunction, contributing to the severe neurological symptoms observed in rabies.
A characteristic cellular change in infected neurons is the formation of Negri bodies. These sharply outlined inclusion bodies are found within the cytoplasm and are composed of viral nucleoproteins (N and P proteins) and viral RNA, serving as sites for viral transcription and replication. While neuronal cell death occurs, it is often not extensive enough to fully explain the rapid onset of fatal neurological symptoms, suggesting that viral interference with neuronal function, rather than mass cell destruction, plays a significant role.
Cellular Basis of Prevention
Vaccination against rabies works by preparing the immune system to recognize and neutralize the virus. Rabies vaccines typically contain inactivated rabies virus or components, most commonly the viral glycoprotein (G protein). When introduced into the body, these viral components are taken up by antigen-presenting cells (APCs).
These APCs then present fragments of the viral glycoprotein to T cells and B cells, which are lymphocytes that play a central role in adaptive immunity. This exposure activates specific B cells to differentiate into plasma cells, which produce virus-neutralizing antibodies (VNAs) that can bind to and inactivate the rabies virus, preventing it from entering host cells. Concurrently, T cells are activated, supporting the B cell response and contributing to cellular immunity, which can help clear infected cells.
Post-exposure prophylaxis (PEP) combines immediate wound care with passive and active immunization. Human rabies immune globulin (HRIG), a passive immunization, provides pre-formed antibodies that offer immediate protection by neutralizing the virus before it can establish widespread cellular infection. This is administered alongside the rabies vaccine series, which actively stimulates the individual’s immune system to produce its own long-lasting antibodies and cellular responses, ensuring protection against future viral invasion.