Viral onset hypothesis

The Viral onset hypothesis is a prominent theory and more than half of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients report falling ill after an acute viral infection. Many different viruses have been researched as possible etiological agents.

Disease onset
Some think there is a single, novel viral agent as yet undiscovered.

Others think many different viruses can initiate and sustain the disease. Viruses linked to disease onset include herpesviruses such as Epstein-Barr virus or HHV-6, enteroviruses such as coxsackie or even influenza (the flu) or a flu-like illness. Many viruses and pathogens have been investigated, with finding being mixed and no particular pathogen found.

There are several hypotheses for how the viral trigger initiates and perpetuates the disease.

Chronic infection
Some think that there may be a low grade, chronic infection whereby the initial virus continues to provoke an immune response, especially in key areas such as the gastrointestinal tract, muscle, and the brain, brain stem, and spinal cord; an example is enterovirus infection.

Autoimmune disease
Some think that symptoms are caused by an inflammatory process that is triggered by an initial infection and continues even after the initial virus is no longer replicating. It is possible that ME/CFS is an autoimmune response that can be triggered by many different infections.

Viral reactivation
Some people think that an immune deficiency allows otherwise common or benign viruses to reactive after lying dormant, for instance HHV-6 and other common herpesviruses have been investigated.

Dysbiosis
Viral infection may trigger intestinal dysbiosis leading to alterations in the immune system and gut-brain axis and causing the symptoms of the disease.

Outbreaks
There have been dozens of reported clusters and outbreaks of ME, which all suggest a role of either a communicable pathogen or in some cases, a toxic agent, however some of these have been non-viral infections e.g. bacterial.

Bacterial and non-viral infections as causes
There are many reports of non-viral infections e.g. bacterial leading to ME/CFS. Some of these have led to reported clusters and outbreaks of ME, for example a water poisoning caused the 2004 Bergen, Norway outbreak and clusters of Q fever infections.

Non-infectious causes
The seminal Dubbo township study in Australia and a number of other very large ME/CFS studies have reported significant numbers of cases that were preceded by non-infectious events, for example serious accidents or injuries, routine vaccinations, or ongoing stress.

Treatment
Antivirals are suggested as a potential treatment, but is known not to be universally effective in ME/CFS.