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HHV-6 Overview - Information supplied by the HHV6 Foundation

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Human Herpesvirus 6 (HHV-6) is an immunosuppressive and neurotropic virus that can cause encephalitis and seizures during a primary infection or when reactivated from latency in immunosuppressed patients. New Research suggests that HHV-6 may play a role in several chronic neurological conditions including MS, mesial temporal lobe epilepsy, status epilepticus and chronic fatigue syndrome. There is an urgent need for more sensitive diagnostic assays and for studies that can prove or disprove the important disease associations that have been suggested. HHV-6 was discovered in 1986 in AIDS patients with cancer and lymphoproliferative disorders.

There are two distinct variants of HHV-6. HHV-6A is the strain most likely to be found in MS, CFS and AIDS and cancer patients. HHV-6B causes roseola, febrile illnesses and encephalitis in infants and reactivates in transplant patients, causing complications such as encephalitis, pneumonitis and liver failure. HHV-6B infects close to 100% of children by the age of two, causing mild flu-like symptoms and rash in some, but occasionally progresses to high fever, encephalitis and seizures. In most cases, the virus goes into latency. However, in patients with impaired immune function, the virus may persist in its active state at low levels for years. While it is generally known that HHV-6 causes roseola and occasional seizures and encephalitis in infants, most physicians do not realize that HHV-6 can persist in a subacute form causing CNS dysfunction. HHV-6 can also cause selective immune suppression and alterations in cytokines that make it more difficult for the body to fend off cancer, intracellular pathogens, viruses and mycobacteria. Finally, HHV-6 has potent transactivating properties that cause it to stimulate other viruses, such as EBV, CMV and HHV-8.

Unfortunately, chronic HHV-6 infections are notoriously difficult to detect with current diagnostic tests. Molecular assays (DNA PCR tests) are useful for acute infections but are not sensitive enough to detect chronic infection because the virus remains active only in the tissues (often the central nervous system). This means there is very little free virus circulating in the serum. Serological assays (tests that look for antibodies instead of virus) are more sensitive but it is difficult to differentiate between active and latent infections since these antibodies fall gradually after an infection and can persist at high levels for several years before falling to lower levels. Also, serological assays cannot differentiate between the A and B variants. In spite of the fact that these antibody tests are imperfect, elevated antibodies may be a patient’s only clue that a chronic infection is ongoing in the CNS, cardiac or other tissues. While an HHV-6 titer of 1:1280, 1:640 or 1:320 in a child or adolescent might be perfectly normal, a titer of this level could be a sign of chronic infection in an adult with clinical symptoms.

HHV-6 is the most common cause of mental confusion in post-transplant patients. HHV-6 limbic encephalitis occurs in approximately 4% of transplant patients resulting in intermittent confusion, poor coordination, flat affect and somnolence.

HHV-6, especially the A variant, can also cause immune suppression. Recent studies indicate that HHV-6 alters immune function by selectively blocking dendritic cell maturation and IL-12 p70 production (Lusso 2005). HHV-6 can cause an elevation in cytokines such as IL-6 contributes to encephalopathy in these patients. (Enoki 2006) While HHV-6B is spread through saliva, the mode of transmission for HHV-6A is not known since it is generally not found in the saliva. In the US, most transplant patients (approximately 97%) reactivate with HHV-6B. In central Africa, however, 44% of infants are found to have variant A. Little is known about the epidemiology of HHV-6A, an infection that is typically acquired later in life. HIV co-discoverer Robert Gallo calls HHV-6A a “progression factor” that speeds the course of an HIV infection to AIDS. Noting that the two “strains” are different enough to be considered distinct viruses, Gallo has proposed that HHV-6B be renamed HHV-9. (Komaroff 2006)


OC Integrative Medical Center
1525 Superior Avenue, Suite 206
Newport Beach, CA 92663
Phone: 949-642-3333
Fax: 949-242-4020

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