Latent Virus Infections

In latent infections, overt disease is not produced, but the virus is not eradicated. This equilibrium between host and parasite is achieved in various ways by different parasites and hosts. The virus may exist in a truly latent noninfectious occult form, possibly as an integrated genome or an episomal agent, or as an infectious and continuously replicating agent, termed a persistent viral infection.

Infectious agents causing chronic persistent infections have found a way of escaping a cell-mediated immune response. The mechanisms include

  1. generation of cells that escape a cell-mediated immune response.
  2. down regulation of MHC production in infected cells so that they are not recognized and destroyed by T cells.
  3. infection of cells in immunoprivileged sites such as the brain.

Examples of latent infection include

  1. Chronic Congenital Rubella, CMV, EBV, hepatitis B, HIV
  2. Latent HSV, VZV, adenovirus and some retroviral infections
  3. SSPE, PML, Kuru, CJD, progressive rubella panencephalitis

1. Chronic Persistent Infections

Enveloped viruses such as paramyxoviruses, some herpesviruses eg. EBV, retroviruses and arenaviruses appear particularly suited to initiate persistent infections. Infection appear to persist because the virus does not disrupt the essential housekeeping functions of the cells. (DNA, RNA and protein synthesis). Some persistently infected cells, such as in measles (SSPE) may be assisted by the capacity of humoral Abs to cap viral Ags on the cell surface. This promotes the shredding of viral Ags from the cell surface, leaving the cell surface free of viral glycoproteins and thus the infected cell is protected from CTLs and K cells.  

2. Latent Occult Viral Infections

Some DNA and RNA viruses, may become undetectable following a primary infection only to reappear and produce acute disease. This latency can be accomplished in different ways.

a. HSV - primary infection usually occurs between 6 to 18 months of age following which the virus persists and cannot be found except during recurrent acute episodes. The form in which the latent occult virus persists is uncertain. Virus cannot be isolated from tissue homogenates, but by cocultivating cells of sensory ganglia with susceptible cells. Virus has been detected in the trigeminal, thoracic, lumbar and sacral dorsal root ganglia. Hybridization studies have detected the viral genome in normal brains as well as peripheral ganglia. These data suggests that the DNA exist in a linear, unintegrated form, perhaps as episomes.

It may be that, as in virus-carrier cultures, infection is confined to only a small proportion (0.01-0.1%) of the ganglion cells because of Abs, CMI, viral interference or metabolic factors. Because there is humoral Abs present, most of the extracellular virus is neutralized and goes undetected. Acute episodes, in which there is a burst of viral replication, probably depends on a transient change in the local level of immunity or changes in the susceptibility of the uninfected cells induced by a variety of physical and physiological factors such as fever, intense sunlight, fatigue or menstruation. The other herpesviruses that infect humans also commonly produce latent infections: VZV in the sensory ganglia, CMV in lymphocytes and macrophages, and EBV in B-lymphocytes.

b. Adenovirus - adenovirus infections in humans are usually self-limiting but the virus frequently establishes a latent, persistent infection of the tonsils and the adenoids. Though these tissues fail to yield infectious virus when homogenized and tested in sensitive cell cultures, cultured fragments of about 85% of these "normal" tonsils and adenoids, after a variable time, show characteristic adenovirus-induced CPE and yield infectious virus. Failure to recover infectious virus initially may be due to the paucity of virions, to their association with either Ab or receptor material, or to the absence of mature virions. The latent infection is probably not the result of lysogeny, since DNA in peripheral lymphocytes appears to be in a linear episomal form.

c. SSPE - latency occurs as a result of incomplete viral production. Immature viral measles virus nucleocapsids are produced.

Latent viral infections affect the incidence and pathogenesis of acute viral disease in several ways. A reactivated virus may spread and initiate an epidemic among susceptible contacts eg. VZV. Viral latency can also be seen in the development of several chronic diseases dependent on the immunological response eg. SSPE and PML. Some latent states induce tumourigenesis.