The Borna virus, specifically Borna Disease Virus 1 (BoDV-1), is a single-stranded, negative-sense RNA virus that infects the central nervous system. Historically, the virus was known primarily as a veterinary pathogen responsible for fatal neurological disease in horses and sheep, particularly in endemic regions of Central Europe. Recent scientific confirmation has established BoDV-1 as the cause of severe, rapidly progressing encephalitis in humans, a condition that carries an exceptionally high case-fatality rate. This discovery shifted the understanding of the Borna virus from a purely animal health concern to a serious, emerging zoonotic threat to human health.
Classification and Primary Hosts
The Borna virus belongs to the family Bornaviridae, which is unique among non-segmented, negative-strand RNA viruses because its replication and transcription occur within the host cell’s nucleus. Classical BoDV-1 is the primary species associated with the historical Borna disease in equids, but the family also includes other zoonotic agents, such as the Variegated Squirrel Bornavirus (VSBV-1). While BoDV-1 has a wide potential host range, its maintenance in nature depends on a specific animal reservoir.
The primary natural reservoir for Borna Disease Virus 1 is the bicolored white-toothed shrew, Crocidura leucodon. These shrews carry a persistent, lifelong infection without showing any obvious clinical signs of illness. The virus is shed by the infected shrews through various excretions, including urine, feces, and saliva, effectively contaminating the environment. The geographic distribution of BoDV-1 in Central Europe, including parts of Germany, Austria, Switzerland, and Liechtenstein, closely mirrors the habitat of the infected shrew populations.
Transmission and Clinical Manifestations
Borna virus infection in humans, horses, and sheep is a zoonotic spillover event. These hosts are accidental “dead-end” hosts that do not transmit the virus further. The infection pathway begins with the shedding of the virus from the persistently infected Crocidura leucodon shrew into the environment. It is hypothesized that accidental hosts become infected through direct contact with the shrew or by inhaling or ingesting aerosolized particles or contaminated food and water containing shrew excreta. The exact entry route into the human body is not definitively proven, but environmental exposure to the reservoir is the presumed mechanism.
Once in a susceptible host, the virus preferentially infects the central nervous system, including neurons, astrocytes, and oligodendrocytes. In horses and sheep, the resulting illness is Borna disease, characterized by behavioral changes such as ataxia, anxiety, aggression, and a fatal, immune-mediated meningoencephalitis. Human infection with BoDV-1 typically manifests as severe, rapidly progressing encephalitis. Symptoms often begin with a non-specific prodromal phase that includes headache, fever, malaise, and fatigue.
The disease quickly progresses to neurological symptoms, which include confusion, disorientation, psychomotor slowing, and ataxia. As the inflammation worsens, patients can develop multifocal myoclonic jerks, seizures, and a rapid deterioration of consciousness, often leading to deep coma within weeks. The case-fatality rate is extremely high, with many confirmed patients dying within two months of symptom onset. Although BoDV-1 was historically linked to certain psychiatric disorders, recent, confirmed cases exclusively demonstrate the virus as the cause of this severe, life-threatening encephalitis.
Detection and Medical Management
Diagnosing Borna virus encephalitis is challenging because of the rarity of the disease and the non-specific nature of the initial flu-like symptoms. Definitive diagnosis requires specialized laboratory testing, which is often performed after other, more common causes of encephalitis have been ruled out. Molecular diagnostic methods, specifically reverse transcription-polymerase chain reaction (RT-PCR or qRT-PCR), are used to detect the viral RNA genome in clinical samples.
The most reliable samples for molecular testing are typically brain tissue, often obtained post-mortem, or cerebrospinal fluid (CSF) collected via a lumbar puncture. Serological testing is also utilized, which involves detecting the presence of antibodies against BoDV-1 proteins, such as the phosphoprotein (P), in the serum and CSF. Early diagnosis using these molecular techniques is important for any potential medical intervention, given the rapid progression of the disease.
Currently, there is no standardized, approved cure for Borna virus infection, and treatment is considered experimental. Broad-spectrum antiviral medications have shown promise against BoDV-1 replication in vitro. The antiviral drug Favipiravir (T-705) has demonstrated potent activity and is used in individual human cases as an experimental treatment. Ribavirin also inhibits BoDV-1 replication, though Favipiravir is generally considered more efficient. Treatment regimens involve aggressive supportive care in an intensive care unit setting alongside the early administration of these experimental antivirals. Prevention relies entirely on avoiding contact with the natural host, particularly shrews or their nesting areas, in endemic geographic regions.