Introduction from the organizers of the 5th International Conference on HHV-6&7

Abstract

Evidence is presented in this journal that the HHV-6 viruses (A and B) not only cause significant immunosuppression, they may play an important role in several neurological diseases including status epilepticus, multiple sclerosis, and a subset of chronic fatigue syndrome cases. Given the staggering implications of these potential disease associations, there is an urgent need for more research to prove or disprove viral involvement. Better diagnostic tests are urgently required since HHV-6 is so difficult to detect in the serum or spinal fluid. In some cases, chronic HHV-6 CNS infections can only be detected by direct brain biopsy when there is no trace of active infection in the peripheral blood or even the spinal fluid. We hope that the data presented at the 2006 Barcelona conference and information contained in this supplement will bring a rebirth of interest to the field. Important questions raised in recent years include: Could a smoldering HHV-6B infection be responsible for a subset of epilepsy cases? Leon Epstein of Northwestern University presented evidence from a multi-center study of status epilepticus in infants, which illustrated that over a third of the cases coincided with primary infections of HHV-6 and another 7% with primary HHV-7. Investigators from the NINDS found that HHV-6 was present in very high copy number in half of mesial temporal lobe biopsies from refractory epileptics had very high levels of HHV-6, especially in the hippocampus, and these infections were localized in the astrocytes. This is consistent with what we know from Carolyn Hall’s studies (Caserta 2004) demonstrating that HHV-6 can persist in the CSF long after it has disappeared from the serum and peripheral blood. Could HHV-6A infection in neural cells be a trigger for MS? Claude Genain writes in this supplement that exposure to HHV-6A but not HHV-6B induces apoptosis in neural cells. He also presented preliminary evidence at the 2006 conference that marmosets infected with HHV-6A (but not HHV-6B) developed MS-type CNS lesions (unpublished data, C. Genain). Other conference abstracts cited increased levels of HHV-6 in patients vs. controls, as detected by PCR, antibody titers and messenger RNA. Could chronic HHV-6 reactivation contribute to chronic CNS dysfunction? Danielle Zerr reports that transplant patients with reactivated HHV-6 often present with CNS dysfunction including depression, cognitive difficulties, and fatigue. Harvard’s Anthony Komaroff writes a thoughtful summary of published evidence from the past 15 years that active infection with HHV-6 is associated with chronic fatigue syndrome (CFS) in a subset of patients, and finds convincing evidence of a role for HHV-6 and other neurotropic viruses. Chapenko presents evidence of increased rates of HHV-6 & 7 co-infections in CFS patients relative to controls. Could HHV-6 antivirals be effective treatment for subsets of patients with MS, CFS or epilepsy? Stanford infectious disease specialists Montoya and Kogelnik report here that six months of valaganciclovir led to dramatic remission in 75% of 12 patients with CFS and mildly elevated antibodies to HHV-6 and EBV. As two publications here describe, there are a number of drugs with good activity against HHV-6. Of special interest, the epilepsy drug lamotrigine (Lamictal) was found to have antiviral activity against HHV-6B. Clinical trials in both MS and epilepsy patients are needed. Does HHV-6A act as a progression factor in AIDS? Immunologist Paolo Lusso summarizes here the mechanisms behind HHV-6 induced immunosuppression. At the conference Lusso and Robert Gallo presented evidence that monkeys co-infected with HHV-6A and SIV progressed to AIDS at a faster rate.