Persistent viral infections are those in which termination of early symptoms and disease is not accompanied by elimination of the virus from the host, but by persistence of viral genetic material in the host. The molecular mechanisms of persistent viral infections are not clearly understood, but three broad conditions must be satisfied for a virus to establish a persistent infection in a host:
Virus must be able to infect host cells without being cytolytic or cytopathic. Viruses have found various cell types such as nonpermissive cells in a host to infect and remain less cytolytic to maintain persistence.
Viral genome must be maintained by various mechanisms. Viral genomes can be maintained in several ways, including integration and extrachromosomal episomes for DNA viruses. However, the mechanisms of viral RNA genome maintenance are not known.
Virus has to avoid detection and elimination by the host's immune system. Viruses have evolved several evasion strategies such as infection of immunologically privileged sites that are not easily accessible to the immune system (central nervous system [CNS] and other sites), antigenic variation, downregulation of immune components, and others. Several viruses cause persistent infection of the CNS because they are not easily detected and eliminated by the host immune response.
Viruses are less cytolytic to cells in which they persist
DNA genomes either integrate or persist as episomes
Mechanisms of persistence of RNA genomes in cells not understood
Avoid detection and elimination by the host
Infect immunologically privileged sites such as CNS
Evidence has accumulated that a variety of progressive neurologic diseases in both animals and humans are caused by viral or other filterable agents that share some of the properties of viruses (Tables 20–1, 20–2, and 20–3). These illnesses have been termed “slow viral diseases” because of the protracted period between infection and the onset of disease as well as the prolonged course of the illness, but a better term is “persistent viral infection.”
TABLE 20–1Conventional Viruses Causing Persistent CNS Infections ||Download (.pdf) TABLE 20–1 Conventional Viruses Causing Persistent CNS Infections
|DISEASE ||AGENT |
|Subacute sclerosing panencephalitis (SSPE) ||Measles virus |
|Progressive panencephalitis following congenital rubella ||Rubella virus |
|Progressive multifocal encephalopathy ||Polyoma virus (JC virus) |
|AIDS dementia complex (ADC) ||Human immunodeficiency virus (HIV) |
|Persistent enterovirus infection of the immunodeficient ||Enteroviruses |TABLE 20–2Unconventional Virus (Prion) Diseasesa ||Download (.pdf) TABLE 20–2 Unconventional Virus (Prion) Diseasesa
|HUMANS ||ANIMALS (PRIMARY HOSTS) |
|Creutzfeldt-Jakob diseaseb ||Scrapie (sheep) |
|Variant Creutzfeldt–Jakob disease ||Transmissible mink encephalopathy (mink) |
|Gerstmann-Straüssler-Scheinker syndrome ||Chronic wasting disease (mule deer, elk) |
|Kuru ||Bovine spongiform encephalopathy (BSE; cows)b |
|Fatal familial insomnia || |
TABLE 20–3Biologic and ...