Latent Infections

All six human herpesviruses are common and important pathogens which establish lifelong latency and may be reactivated at any time. When the trigger is profound immunosuppression, for example, in AIDS or organ transplantation, reactivation of a latent herpesvirus infection may be lethal. Paradoxically, although all herpesviruses share the common lifestyle of latency, they have evolved divergent strategies for achieving that end A key distinction is that herpes simplex and varicella-zoster viruses persist in neurons, which are nondividing but long-lived cells, whereas cytomegalovirus, EB virus, and human herpesvirus 6 persist in lymphocytes, which are dividing but short-lived (Table 10-1),

The state of the genome is a central consideration in latency. With some species of viruses the genome must become integrated into a cellular chromosome, whereas for others it survives satisfactorily as a free plasmid (episome) in the cytoplasm or nucleus. Of course, it is essential that any latent viral genome, whatever its physical state or location, be complete if it is ever to be able to program the replication of viable virus following subsequent reactivation (in contrast with the oncogenic potential of many defective viral genomes which may induce cancer following integration even though incapable of further replication). However, the expression of the latent genome is, by defi-

it is better described as a chronic infection with continuous low-level virus production (see below).

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a rare, lethal manifestation of reactivation of an almost universal latent infection with human JC polyomavirus. The acute infection generally occurs in childhood and is usually subclinical, or there may be mild respiratory disease. The virus then persists for life in the kidneys, and perhaps also in the brain or elsewhere, and is shed in urine from time to time, especially during pregnancy or immunosuppression. Almost nothing is known of the mechanism of establishment and maintenance of latency. The PML condition is a demyelinating disease of the brain {see Fig. 18-4), seen only in severely immunocompromised individuals, especially AIDS patients, organ transplant recipients, and those with advanced disseminated lymphoid malignancies. The target cell is the oligodendrocyte, not the neuron.

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