Immunity to Viruses

One of the major functions of the body's immune system is to mount an effective immune response against tissue invasion by microorganisms such as viruses. For a virus to persist, it needs to adopt one or more mechanisms to avoid immune elimination.

Previously Described Immune Escape Mechanisms

Repressed Expression of Viral Antigens For example, the genome of Epstein-Barr virus (EBV) is generally limited in its expression in B lymphocytes. Also, street rabies is relatively slow in evoking protective immunity, allowing time for the virus to travel to the central nervous system.

Repressed Expression of Cellular Antigens Viral genes can suppress expression of host cellular components required for efficient immune recognition of viral-infected cells. For example, the EBV genome can down-regulate the production of both class I major histocompatibility antigens and cellular adhesion molecules.

Destruction of the Immune System This mechanism is employed by HIV which can incapacitate the immune system by directly infecting and destroying T lymphocytes. Also HHV-6 may be able to infect and destroy the precursors of natural killer (NK) cells.

Inhibition of Immune Function This is seen, for example, in the diminished lytic activity of lymphokine activated killer cells (LAK) following contact with herpes simplex infected fibroblasts.

Congenital Infection When viral infection occurs prior to the maturation of the immune system there can be an inability to discriminate between self and viral antigens. This can lead to life-long infection as in the case of congenital hepatitis B virus (HBV).

Antigen Deletion/Mutation

We have sought evidence for an additional mechanism by which viruses may avoid immune elimination. It is for the virus to either delete or mutate the major immunogenic components. Such "down-sized" viruses would presumably be less efficient in replicative and assembly functions but would gain an advantage by being able to sneak past an indifferent cellular immune system. The existence of this mechanism was revealed in early studies on patients with chronic fatigue syndrome and in patients with more severe encephalopathies. We have proposed the term "Stealth" to best describe these viruses which characteristically evoke little or no in vivo inflammatory reaction and are not readily detected using conventional viral cultures and immunological techniques.

Definition of a Stealth Virus

Stealth viruses are defined as cytopathogenic viruses which are able to establish a persistent infection because of deletion and/or mutation of genes which, if present, would code for immunogenic components able to evoke an anti-viral inflammatory response. As a consequence of this adaptation, stealth viruses are difficult to detect in vivo and require special efforts for successful in vitro cultivation.