Neurotropism

Neurotropism (from Greek neuron — nerve and tropos — direction, property) is the specific biological ability of certain viruses and bacteria to selectively affect and infect cells of the central and peripheral nervous systems and survive within them (neurons and glial cells).

Etiology and pathophysiology

The human brain is protected by a powerful physiological shield—the blood–brain barrier (BBB), which prevents most toxins and microorganisms in the blood from entering it.

Viruses that infect nerve cells are termed neuroinvasive, whereas those capable of causing diseases of the nervous system are termed neurovirulent. These characteristics vary from one virus to another, may occur in combination, and sometimes one may predominate.

Neurotropic viruses (herpes simplex virus, rabies virus, enteroviruses) have evolved unique mechanisms to circumvent this protection:

• retrograde axonal transport — the virus enters a nerve ending in the skin or muscle (e.g., following an animal bite). It then binds to specialized transport proteins within the nerve fiber (axon) and travels upward, as if along rails, reaching the spinal cord and brain;
• penetration via the bloodstream — after entering the body, poliovirus enters the bloodstream, crosses the BBB, and affects the motor neurons of the anterior horns of the spinal cord and the cranial nerve nuclei;
• “Trojan horse” route — the virus (e.g., coronavirus) enters brain tissue directly “under cover,” either along olfactory nerve fibers or within immune cells (macrophages) that normally cross the BBB.

Clinical significance

Neurotropism determines the severity and specific characteristics of the disease. After entering the nervous system, the pathogen may cause acute inflammation with cellular destruction (encephalitis, meningitis, paralytic poliomyelitis).

Herpes simplex virus, which has low neuroinvasiveness but high neurovirulence, enters a lifelong latent state in the nerve ganglia.

Some infections caused by neurotropic viruses are associated with a high risk of mortality and neurological deficits (residual neurological sequelae) following recovery.