Viruses, brain and immunosuppression

There are a number of viruses which affect the central nervous system in a variety of ways. One group, which includes rabies virus and the agents of the arthropod-borne encephali tides, causes brain disease as its primary effect. Another group, including polio virus, affects the brain secondarily to more generalized infection in certain individuals. An encephalitis may result directly from invasion of the brain by virus, but it may also occur in the absence of such invasion following infection of other organs with certain viruses (including measles, rubella, cytomegalo virus and many respiratory viruses). There is also a group of viruses, including the herpes viruses and the human papova viruses BK and JC, which establishes persistent or latent infections in the host, and it is this group of viruses that is of greatest importance with regard to the immunocompromised individual. Obvious immunodeficiency can be induced by prematurity, inborn defects (such as severe combined immunodeficiency, thymic hypoplasia and ataxia-telangiectasia), neoplasias and malnutrition. Normal states, such as the neonatal period, pregnancy and old age, also alter the immune state of the individual (Oleske & Minnefor, 1980). There is also an increasing number of individuals who are being therapeutically immunosuppressed in the course of their treatment for leukaemia, or after receiving transplanted organs, and it is with this group that we have been most concerned. Many viruses take advantage of a host's impaired immunity. For example, herpes viruses, vaccinia and wart viruses are commonly found in cell-mediated immunodeficient states, while picorna viruses, hepatitis 'B ' and influenza viruses are more influenced by poor antibody-mediated immunity. Viral infections themselves may significantly depress the host's defence system, and concurrent viral infections have been associated with more severe or prolonged infection in such individuals. This is illustrated by the fatal dual infections with adeno virus and influenza virus that have been reported in some children (Oleske & Minnefor, 1980) and recurrent HSV1 infections with colds. Immunosuppression not only makes the host more susceptible to viral infection but, by inhibiting the immune mechanisms of the host, creates conditions suitable for the persistence of virus in the central nervous system. Indeed, viruses that produce latent or persistent infections are the ones most frequently associated with illness in the immunocompromised patient. The human papova viruses BK and JC, originally isolated from transplant recipients, are infrequent but important hazards in the management of the immunocompromised. BK virus establishes latent or persistent infections in the kidneys, and excretion of the virus, often accompanied by ureteric stenosis, is a frequent occurrence following renal transplantation. JC virus is believed to establish latent infections in the brain, and when reactivated in a immunocompromised host may give rise to the relentless degenerative disease progressive multifocal leukoencephalopathy. Mercifully, this disease is rare, with an incidence of only one per million of population per year. It has recently been reported in two people suffering from Acquired Immunodeficiency Syndrome (Miller et al. 1982; Bedri et al. 1983). Members of the herpes virus group are those most frequently diagnosed as causing serious disease in the immunocompromised individual, and include cytomegalo virus, varicella-zoster virus, herpes simplex virus (HSV) types 1 and 2, and Epstein-Barr virus. However, with regard to central nervous system involvement, HSV 1 is of most interest. The idea that recurrent herpetic disease involves reactivation of latent infection in the sensory ganglia is not new; indeed, such a model was proposed by Goodpasture in 1929. There have since been many demonstrations, using the methods of co-cultivation and explantation, that HSV can be harboured in the sensory and autonomic ganglia of man (Warren et al. 1977, 1978; Baringer,