Bornavirus - Neurotropic virus of interest in human and animal pathology: Molecular diagnosis (PCR). 

Information 01-05-2018. 

Bornaviruses are a family of unsegmented, single-stranded and negative RNA viruses (-ssRNA) of the Mononegavirales order. They are neurotropic viruses that affect a wide range of hosts, including birds, mammals and reptiles, and also, isolated cases of infection in humans have been reported. According to its genome, phylogenetic data and biological characteristics have been classified into different species, which are described below.

Bornavirus species that affect mammals include the classic Borna disease virus -1 and -2, BoDV-1 and -2 (Mammalian 1 bornavirus), and the recently discovered variegated squirrel bornavirus, or VSBV- 1, due to its acronym in English (Mammalian 2 bornavirus).

BoDV-1 is the causative agent of Borna disease (BD), first described in the 18th century and named after the city of Borna, near Leipzig, Germany, where a fatal epizootic neurological disease was described between military horses. Borna disease affects horses and sheep more frequently. However, many species of mammals including farm animals (cattle and goats), zoo animals (llamas, hippos, alpacas, monkeys, etc.) and, rarely, pets (dogs and cats) can also be affected. Subsequently, a single case of lethal infection was detected with a divergent bornavirus called Borna-2 disease virus (BoDV-2). Currently, it is believed that the natural reservoir of BoDV-1 is the bicolor shrew of white teeth (Crocidura leucodon), and that the disease in large mammals is only an accidental event. However, due to the fact that the habitat of this animal is reserved for central Europe, it is believed that there must be other animals that act as a natural reservoir of the BoDV in other areas. In C. leucodon, the virus replicates in a large number of tissues and is excreted in different ways. In larger mammals, such as horses, sheep and other domestic mammals, the infection is selectively neurotropic, and triggers a massive infiltration of T cells into the central nervous system (CNS), causing meningoencephalitis with characteristic clinical signs and an almost inevitable lethal outcome. The incubation period in animals varies from two weeks to several months. The infection can lead to a severe neurological disorder characterized by an acute or subacute disease with meningoencephalitis, or mild manifestations with impaired nerve cell functions. Disease-specific syndromes depend on many factors of the host, including the species, breed, age and immunological status of the animal at the time of infection. Depending on the animals, the infection of the virus can induce various behavioral and neurological abnormalities. Paralysis is common and death occurs within 1-5 weeks in most animals. Recovery is possible with altered behavior for life.

In early 2018, the BoDV-1 virus was associated with four cases of human disease in Germany, resulting in the death of three people. Three of the cases belonged to a group of solid organ recipients from a single donor, with no evidence of any clinical manifestation of the disease, and the other case, responded to an isolated BoDV-1 encephalitis. Infection with BoDV-1 in humans occurs strangely; however, taking into account the severity of the disease, one should consider adding BoDV-1 to the list of pathogens included in the differential diagnosis of the causes of human encephalitis and the possibility of transmission through donated organs, especially in areas where Borna's disease is endemic. The routes of transmission of BoDV-1 to humans from the animal reservoir remain unknown.

In addition to the classic bornavirus, a new bornavirus, the VSBV-1 (Mammalian 2 bornavirus), isolated from the central nervous system of three keepers of variegated squirrel (Sciurus variegatoides), which had encephalitis, was discovered and died between 2 and 4 months after the onset of symptoms (fever and/or chills, confusion, unsteady gait, myoclonus and/or eye paresis, progressive psychomotor retardation and coma). The virus was also found in the squirrels under its care, and since then, in multiple animals of that species, increased attention of the scientific community on this viral family.

Unlike mammals, birds infected with Bornavirus have a clinical presentation that involves the gastrointestinal tract, in addition to the most typical neurological deficits. Avian bornaviruses are the etiologic agents of proventriculus dilatation disease (PDD), an infectious, progressive, and often lethal disease of birds. The PDD affects more than 80 species of psittacines, where its clinical importance is concentrated, but also toucans, honeycreepers, weavers finches, water birds, raptors and passerines. Within avian bornaviruses species are differentiated, Psittaciform 1 bornavirus, Passeriform 1 bornavirus, Passeriform 2 bornavirus and Waterbird 1 bornavirus. In addition, some isolated bird viruses remain unclassified due to lack of information about them.

Proventriculus dilatation disease was recognized for the first time in the early 1970s in macaws exported to Europe and North America from Bolivia, and has now spread to Australia, Latin America, Japan, the Middle East and Africa. The name of the disease derives from the predominant clinical characteristic of the disease in parrots. The characteristic lesions observed in these birds include encephalitis and macroscopic dilatation of the anterior part of the stomach: the proventriculus. The proventriculus dilation occurs due to the accumulation of food, secondary to defects in intestinal motility caused by the virus. The intestinal dysfunction is probably due to an immune damage induced by the viruses on the autonomic nerves of the upper and middle gastrointestinal tract. The disease is also associated with central nervous system damage. PDD is a complex disease and the affected birds can present diverse clinical signs. In the classic form of the disease, the signs belong to the slow emptying or total blockage of the movement of the intake through the proventriculus. As a result, the proventriculus dilates and the birds begin to regurgitate the ingested food, lose weight, and finally die of starvation. Alternatively or additionally, birds may exhibit neurological signs, especially reflected as inability to fly or perch, or as loss of vision. Other symptoms different from the classic form include sudden death due to heart failure, as a result of severe myocarditis, or nonspecific neurological signs, such as ataxia and torticollis. In addition, not all infected birds develop an immediate clinical disease. Many birds infected with bornaviruses can survive as healthy carriers for years and then die unpredictably from PDD. This is especially true in the case of waterfowl, where outbreaks of clinical disease appear to be random and sporadic despite a relatively high prevalence of infection. The mechanism of transmission of PDD is not entirely clear, but it is believed that avian bornavirus is transferred mainly from one individual to another through direct or intimate contact, or via fecal-oral, by exposure to infected fecal material. Because of this, it spreads easily in birds in captivity.

Finally, the species Elapid 1 bornavirus, which causes disease in snakes, has been designated as another species within the family Bornaviridae, but not included in the genus Bornavirus, contrary to the species described in mammals and birds. In addition, the existence of other bornaviruses is known in reptiles, still pending classification to await having more information available.

The diagnosis of infection by different viruses of the Bornaviridae family can be done by serological methods or by molecular methods such as the reverse transcriptase polymerase chain reaction (RT-PCR) method. RT-PCR with reverse transcriptase is an efficient, rapid, sensitive and specific method that does not require infected animals or humans to develop complete immune responses. Therefore, PCR is especially suitable for the early detection of the virus.