Coronaviruses as Encephalitis - Inducing Infectious Agents

Encephalitis usually refers to brain inflammation of various possible causes, including viral infections. Overall, viruses represent the most common cause of encephalitis in humans. The U.S. Center for Disease Control and Prevention (CDC) estimates an annual incidence of usually between 150 and 3000 new cases per year of Arboviral encephalitis in the United States (http://www.cdc.gov/). Although several thousand cases of encephalitis of various viral origins are reported each year, the CDC suspects that many more cases may go unreported. Indeed, encephalitis can follow or accompany common viral illnesses, such as infectious respiratory diseases, and sometimes signs and symptoms of the latter may mask concurrent encephalitis. Most commonly, clinically relevant viral encephalitis affects children, young adults, or elderly patients. The involvement of other determinants, such as the nature of the specific viral agent, the host immune status, and various genetic and environmental factors, is also of importance. The pathophysiology of viral encephalitis varies according to the virus family involved. Encephalitis occurs in two forms: primary encephalitis involving direct viral infection of the central nervous system (CNS; brain and spinal cord) and secondary encephalitis involving a viral infection which first occurs elsewhere in the body and then travels to the brain. Viruses may enter the CNS through two distinct routes: hematogenous dissemination or neuronal retrograde dissemination. The hematogenous spread, which is the most common path, involves the presence of a given virus in the blood (viremia), where it can either remain free for a period of time or infect leukocytes that will become some sort of viral reservoir. This latter situation, called the Trojan horse, is the route taken by human immunodeficiency virus (HIV) to disseminate to the CNS in humans. Arboviruses also use the hematogenous route to gain access to the CNS, where they can induce a zoonotic encephalitis, with the virus surviving in infection cycles involving bites by arthropods and various vertebrates, especially birds and rodents. After an insect bite, the virus can be transmitted in the blood of a susceptible animal after local replication in the skin. Another form of viral spread towards the CNS is through retrograde neuronal dissemination, where a given virus infects neurons in the periphery and uses the transport machinery within those cells in order to gain access to the CNS. Neuroinvasive viruses can damage the CNS as a result of misdirected host immune responses (virus-induced neuroimmunopathology) and/or viral replication, which will