Yellow fever is a viral illness transmitted by infected mosquitoes, causing symptoms ranging from mild fever to severe liver disease. Caused by a virus from the Flaviviridae family, it is found in tropical regions of Africa and South America. Although a vaccine exists, outbreaks continue to be a public health concern. The disease’s name comes from the jaundice, or yellowing of the skin and eyes, that can develop from liver damage in severe cases.
Viral Entry and Initial Target Cells
The infection begins when an infected mosquito bites a human, introducing the virus into the bloodstream. The virus first seeks out specific immune cells, with its primary targets being dendritic cells and macrophages. These cells are strategically located in the skin and lymph nodes to detect foreign invaders.
Upon encountering these cells, the virus initiates entry. Its surface proteins act like keys, designed to fit into receptor proteins on the surface of dendritic cells and macrophages. Once attached, the host cell is tricked into engulfing the virus through a process called endocytosis.
By infecting the cells meant to orchestrate an immune response, the virus can replicate while dampening the body’s alarm systems. Infected dendritic cells then travel from the skin to nearby lymph nodes. This migration helps the virus spread into the lymphatic system and, eventually, the wider circulatory system.
Hijacking the Cellular Machinery
Once inside a host cell, the Yellow Fever Virus begins replication. The virus sheds its outer coat, releasing its genetic material—a single strand of RNA—into the cell’s cytoplasm. This viral RNA commandeers the host’s equipment, forcing the cell to prioritize making viral components.
The viral RNA is translated by the cell’s ribosomes into a long protein chain, which is then cut into smaller, functional viral proteins. These proteins build new virus particles and form a replication complex. This complex is where the virus makes thousands of copies of its RNA genome, a process concentrated in the endoplasmic reticulum.
The virus remodels the endoplasmic reticulum, creating protected pockets where replication can occur shielded from cellular defenses. Within these compartments, new viral genomes and proteins are produced and self-assemble into new virus particles. This turns the infected cell into a factory for producing a new generation of viruses.
Hepatocyte Infection and Damage
After multiplying in the lymph nodes, the virus travels through the bloodstream to invade the liver’s main cells, known as hepatocytes. The liver’s rich blood supply and specific surface receptors make it particularly vulnerable. This stage of infection is responsible for the most severe symptoms of yellow fever.
Inside the hepatocytes, intense viral replication disrupts normal liver function and triggers a cellular self-destruct sequence called apoptosis. As the infected hepatocytes die, they shrink and form dense masses known as Councilman bodies. These remnants are a distinctive microscopic feature of yellow fever and a clear indicator of severe organ damage.
The widespread death of hepatocytes severely compromises the liver’s ability to filter toxins, produce clotting factors, and process bilirubin. The failure to process bilirubin causes the characteristic jaundice. The loss of clotting factors contributes to the hemorrhagic symptoms, such as bleeding from the nose and mouth, that define the toxic phase of the disease.
Cellular Mechanisms of Immunity and Vaccination
The body’s immune system responds to the viral assault. Specialized immune cells called T-cells are trained to recognize signs of viral infection on other cells. When cytotoxic T-cells identify an infected hepatocyte, they induce it to undergo apoptosis, eliminating the viral factory to control the infection’s spread.
Simultaneously, B-cells begin to produce antibodies. These proteins are designed to bind to the Yellow Fever Virus, neutralizing it so it can no longer enter host cells. This natural immune response clears the virus from the bloodstream and is what allows most people to recover.
The yellow fever vaccine contains a weakened (attenuated) version of the virus and works by stimulating this same immune response without causing disease. This limited infection is enough to activate both T-cells and B-cells, prompting the creation of long-lasting memory cells. These memory cells provide durable immunity, ready to quickly neutralize the real virus upon any future exposure.