Human Herpes Virus 6 (HHV-6) is a very common virus which infects most children by the time they are 2 years of age. HHV-6 causes roseola with associated fever and skin rash in about 30% of babies. It rarely causes significant immediate problems and is almost never fatal. It is a very infectious agent, which is probably transmitted through saliva.
HHV-6 was discovered in 1986. It is a member of the herpes family of viruses, a group which also includes Herpes Simplex Virus-1 and -2, which cause cold sores, Epstein-Barr virus, which causes infectious mononucleosis, and Varicella-Zoster Virus, which causes chicken pox.
Human Herpes Virus 6 is of interest to multiple sclerosis (MS) because several studies have found indicators of the virus to be significantly higher in people with MS (PwMS) than in control subjects. This link is controversial - some commentators allege that HHV-6 is the cause of the disease, others that it is merely an opportunist invader, while still others discount its role altogether.
People with multiple sclerosis have been found to have higher levels of anti-HHV-6 antibodies than control subjects [Caselli et al, 2002 and Soldan et al, 1997], more HHV-6 DNA in blood serum [Álvarez-Lafuente et al, 2002, Tejada-Simon et al, 2002 and Tomsone et al, 2001] and evidence of active HHV-6 infection more often [Chapenko et al, 2003 and Álvarez-Lafuente et al, 2002]. None of these studies found these HHV-6 markers in all the subjects with MS and all the markers were found in some of the control subjects.
Another study found higher levels of HHV-6 DNA from PwMS during relapses than those who were in remission [Berti et al, 2002], although another study was unable to detect a difference [Alvarez-Lafuente et al, 2002].
A study of people with multiple sclerosis in Kuwait failed to find evidence of HHV-6 DNA in the blood of a small sample of people with MS [Al-Shammari et al, 2003].
Attempts to find active HHV-6 in cerebrospinal fluid (CSF) or other CNS tissue have been mixed. Some studies have been successful [Goodman et al, 2003, Cermelli et al, 2003, Tejada-Simon et al, 2002 and Knox et al, 2000] but others have failed to replicate these findings [Rodriguez Carnero et al, 2002 and Gutiérrez et al, 2002].
One way that HHV-6 might be involved is through a mechanism called molecular mimicry. It is proposed that a small section of one of the HHV-6 proteins resembles a small section of one of the proteins in myelin - the insulating substance around brain cells that is damaged in multiple sclerosis. This resemblance means that our immune systems are unable to differentiate between the two and mistakenly attack the myelin as well as the virus. One study has identified a candidate section in one myelin protein, called Myelin Basic Protein (MBP), and showed it to be activated by an HHV-6 protein in people with MS [Tejada-Simon et al, 2003]. However, another laboratory failed to show any increased ability of HHV-6 to activate MBP-reactive T cells in PwMS [Cirone et al, 2002].
It has also been suggested that protein produced by HHV-6 attracts certain immune system cells (macrophages and monocytes) [Luttichau et al, 2003]. Perhaps it does this so that it can infect them but these researchers suggest that this function is also involved in the multiple sclerosis disease process.
Another way HHV-6 might be involved in MS is via a cell surface protein, called membrane cofactor protein (CD46). CD46 is responsible for regulating a branch of the immune system, called complement, and preventing complement activation on the bodies own cells. However, CD46 has also been identified as the cellular receptor for HHV-6 [Santoro et al, 1999]. Elevated levels of soluble CD46 have been found in both the blood and the cerebrospinal fluid of people with MS [Soldan et al, 2001].
Human Herpes Virus 6 Links:
Human Herpesviruses 6 and 7
Institute for Viral Pathogenesis
Multiple Sclerosis HHV-6 Link
Clue to Viral Trigger in MS?
Does Human Herpesvirus 6 Cause Multiple Sclerosis?
Infectious Links to MS Questioned
Human Herpes Virus 6: A New Public Threat?
Active Human Herpesvirus Six and Multiple Sclerosis
Human herpesvirus 6
Active HHV-6 Infections in Patients with Early MS
HHV-6 in CSF Can Cause Encephalitis After ASCT