Human Herpesvirus Six

Wisconsin Viral Research Group, Ltd.

About HHV-6

What is Human Herpesvirus 6 (HHV-6)?

HHV-6 one of the eight known members of the human herpesvirus family.
Note that HHV-6 is not the virus that causes cold sores, genital herpes, chicken pox, shingles, or infectious mononucleosis.

Primary Infection

HHV-6 was first discovered in 1986 in the United States at the National Cancer Institute. This virus infects human white blood cells, specifically T lymphocytes.

Researchers have identified HHV-6 as the cause of childhood roseola (exanthem subitum). Symptoms of this illness include fever and a distinct type of rash. Most infants are infected with HHV-6 before age two, but many display mild or no symptoms. Some symptoms, such as fever, may be incorrectly attributed to conditions other than roseola. However, a small number of infected infants can develop serious disease including bone marrow infection (decreased production of white blood cells and platelets) and brain infection (seizures).

Serologic testing reveals that more than 95% of the world's population is positive for antibodies to HHV-6, indicating an immune response to an infection by the virus. Transmission of this virus is believed to occur as a result of exposure to saliva.

After this initial infection, HHV-6 viral DNA remains latent, or dormant, within the nuclei of cells.

The Biologic Repertoire of HHV-6

The best data about HHV-6 disease comes from children with roseola. Symptoms noted in infants with roseola include fever, swollen glands, lethargy (fatigue), nervous system complications, and bone marrow suppression.

HHV-6 is also known to infect and destroy the cells that produce myelin, the fatty coating that surrounds and protects nerve cells. Additionally, the virus demonstrates the ability to cause disruption of the normal functioning of the human immune system.

HHV-6: Variants A and B

Two variants of HHV-6 are recognized: HHV-6A and HHV-6B. Primary infection of HHV-6B is the cause of roseola in children and greater than 95% of the population has antibodies to this variant. Primary infection with HHV-6A is believed to occur later in childhood or during adulthood and may occur without symptoms.

Latency and Reactivation

HHV-6 reactivation in adulthood can result in illness. Reactivation means that the virus is no longer dormant and begins to replicate. In most individuals, reactivations are extinguished by the immune system and the virus is forced back into latency. Click diagram below to enlarge.

Reactivations in Persons with Intact Immune Systems

The factors that lead to reactivation in people with intact and functioning immune systems are unclear and probably include genetic and environmental causes (such as hormones, other infections, and exposure to chemicals). Most instances of reactivation will not result in chronic, active infection as the normal immune system will suppress the reactivated virus and return it to a latent state. However, reactivation of HHV-6 in normal adults has been associated with a mononucleosis syndrome, autoimmune disorders, and nervous system diseases.

Recent studies have revealed active HHV-6 infections in single, random blood samples taken from Multiple Sclerosis (MS) patients (56% positive) and Chronic Fatigue Syndrome (CFS) patients (39% positive). Normal, healthy controls were negative for active HHV-6 virus (0% positive). This is a significant finding and demonstrates that active HHV-6 infections are not seen in healthy people without these disease associations.

HHV-6 and MS HHV-6 and CFS

Reactivations in Persons with Compromised Immune Systems

In individuals whose immune systems have been compromised by disease (e.g. AIDS) or treatment (e.g. chemotherapy for cancer or immunosuppressive drugs after transplantation), a reactivation of HHV-6 can result in suppression of the bone marrow or inflammation of the tissues of the brain, liver or lungs.

HHV-6 and Transplantation

Why is the Wisconsin Viral Research Group interested in HHV-6?

Work from several laboratories has strongly implicated HHV-6 as the cause of multiple sclerosis.
Other studies have suggested a role for HHV-6 in many cases of severe, persistent fatigue especially in patients with other signs of systemic disease (fever, swollen lymph nodes, cognitive impairment).
HHV-6 associated disease has been successfully treated with antiviral medications.
Recognition of the presence of active HHV-6 infections in MS, CFS, and other chronic diseases would allow for treatment of these patients.