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 the persistence of viral genome in the host. Persistent viral infections could be latent infection, in which viral genome is maintained without making any infectious virus particles or chronic infection, where a low level of virus is made without causing any or little damage to the target tissue. Three main conditions must be fulfilled for a virus to cause persistent infection, including little to no cytopathic effect of the virus to the host cells, maintenance of viral genome in the host cell, and avoid elimination by the immune system. Several viruses have utilized these strategies to persist in an immune-privileged site, the central nervous system (CNS), and over time after reactivation cause rare disease in the CNS or distant sites. These viruses include measles, rubella, enterovirus, HIV, JCV, HSV 1, 2, and VZV. In addition, nonconventional agents such as prions (infectious prion proteins, PrPsc) cause slow degenerative diseases of the CNS such as Creutzfeldt-Jakob disease (CJD) and others. These persistent viral agents and prions and the diseases they cause will be discussed in this chapter.
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 cytopathic or noncytolytic to maintain persistence. For example, herpes simplex virus (HSV) remains latent in sensory neurons; HIV is less cytopathic to resting T cells or monocytes/macrophages.
Viral genome must be maintained by various mechanisms. Viral genomes can be maintained in several ways, including integration of retroviral DNA (HIV) and extrachromosomal episomes for DNA viruses (HSV). However, the mechanisms of viral RNA genome maintenance are not known.
Virus must 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 such as the 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. Many of the persistent viruses employ some or all strategies to avoid elimination by the immune system.
❋ Viruses must be less cytolytic to cells in which they persist
❋ DNA genomes either integrate or persist as episomes
Persistence of RNA genomes not understood
❋ Antigenic variation, immune components downregulation, infection of immune-privileged sites such as CNS allow viral persistence
How does antigenic variation allow the virus to escape elimination?