Neurovirology is an interdisciplinary field which represents a melding of clinical neuroscience, virology, immunology, and molecular biology. The main focus of the field is to study viruses capable of infecting the nervous system. In addition to this, the field studies the use of viruses to trace neuroanatomical pathways, for gene therapy, and to eliminate detrimental populations of neural cells.
Overview The field of neurovirology was formed within the past 30 years. It was founded upon the discovery that a large number of viruses are capable of invading and establishing latent infections in nervous tissue, but also causing life-threatening acute infections . Such viruses have been shown to produce acute and slow, chronic, or progressive nervous system diseases including neurodegenerative diseases and cognitive disorders . Neurovirology incorporates the related fields of virology, neuroscience, neurology, immunology, and molecular biology. The main focus of the field is to study the molecular and biological basis of virus induced diseases of the nervous system. In addition to this, the field studies the use of these viruses as tracers of neuroanatomical pathways and as vectors for gene therapy. The field relies upon neuroimaging, isolation of the virus from brain tissue or CSF, serological testing of serum and CSF, and microscopic examination of tissue to diagnose nervous system infections.
History Neurovirology only became an official field within the past 30 years. However, the true origin of neurovirology can be accredited to the discovery that some viruses may have an affinity for nervous system tissue. This discovery was made in the late 1880s with research involving rabies. In 1881, while studying rabies, Louis Pasteur demonstrated that the central nervous system played a crucial role in the progression of the disease. Following this discovery, in 1890, Schaffer demonstrated histological evidence that the rabies virus spread via neural networks. In 1929 Heinrich Pette established the first classification criteria for inflammatory diseases of the nervous system. This classification separated the diseases into two groups: gray matter acute and white matter acute inflammatory diseases. Gray matter acute inflammatory diseases were characterized by damage to neurons with myelin remaining intact. White matter acute inflammatory diseases were characterized by destruction of the myelin, with neurons remaining intact. In 1938, Sbin and Olitsky discovered that the distribution of the virus within the body depended on its mechanism of entry. In 1965, ZuRhein and Chou established that destruction of myelin could result from primary virus infection, not only from autoimmune response to the virus. Most of the research of which the field of neurovirology is based upon occurred in the late 1980s and the 1900s. Beginning in 1999 the International Society of Neurovirology has recognized and awarded individuals who have contributed significantly to the field with the Pioneer in NeuroVirology Award.
Major viruses studied
DNA virus family
Herpesviruses Herpes simplex virus type 1 (HSV-1) Evidence may support link between virus and Alzheimer's disease, intractable focal epilepsy, and acute disseminated encephalomyelitis Infection can produce myelitis and encephalitis Herpes simplex virus type 2 (HSV-2) Infection can produce myelitis and encephalitis Human cytomegalovirus (CMV) Infection is associated with Guillain–Barré syndrome Is the most common viral cause of childhood intellectual disability Is linked to neurological abnormalities, such as: microencephaly, seizures, hypotomia, and sensorineural hearing loss Varicella-zoster virus (VZV) Is associated with neurological complications such as: meningoencephalitis, myelitis, cerebellar ataxia, Reye's syndrome, cranial neuropatheis, and postinfectious disseminated encephalomyelitis Epstein-Barr virus (EBV) Is associated with Guillain–Barré syndrome, cranial mononeuropathies, focal encephalitis, and myelitis Is considered the leading viral candidate for causing multiple sclerosis Human herpesvirus type 6 (HHV-6) and Human herpesvirus type 7 (HHV-7) Have not been linked to human nervous system disease
Polyomaviruses JC virus (JCV) Is associated with progressive multifocal leukoencephalopathy and demyelination
RNA virus family
Rhabdoviruses Rabies virus Gives rise to neuronal dysfunction
Paramyxoviruses Measles virus Is a major cause of neurological deficits Mumps virus Is the leading cause of virus induced aseptic meningitis and encephalitis
Retroviruses Human immunodeficiency virus (HIV) Is associated with cognitive dysfunction
Viral entry into the nervous system Viruses have evolved mechanisms enabling them to easily infiltrate the nervous system. Two main methods of viral entry have been identified: transneuronal spread and hematogenous spread.
Transneuronal spread The mechanism behind transneuronal spread is not entirely known yet, but it involves the virus escaping the immune system by traveling up the axons of the nerves.
Hematogenous spread There are two main ways that a virus is thought to enter the brain via hematogenous spread. The first is by infecting an immune cell, which then carries the virus to the nervous tissue. Viral examples of this include the JC virus which infects B cells and HIV which infects CD4 T cells and macrophages to infiltrate the brain. The second is by crossing the blood capillaries as a free virus or in leukocytes.
Advantages of infecting the nervous system Neurons lack molecules necessary to present viral peptides on the surface to killer cells, which means they provide a safe house for viruses to replicate. Once viruses get in neurons they can persist for the hosts lifetime and can influence the factors that disturb the function of neurons and the homeostasis of the nervous system, leading to nervous system diseases.
Tools used for diagnosing neuroviral infections There are several diagnostic tools which have become invaluable to diagnosing viral infections of the nervous system. In the past, more invasive methods of obtaining samples for diagnosis were needed such as the use of brain biopsy. Now, with the advancement of technology, less invasive means are used more frequently, such as neuroimaging and the analysis of cerebrospinal fluid (CSF).
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