A perspective on human herpes virus 6 (HHV-6).

For its relatively short “life span” HHV-6 has had an interesting and complex history right from the start. It was first called HBLV (B for B-cells), because we repeatedly found it in association with B-cell lymphomas in HIV infected people. We changed it to HHV-6 when we learned it was chiefly pan T-cell tropic and neurotropic. Then of course came the division into HHV-6A and HHV-6B cell strains, followed by the finding of HHV-7. Concomitant with this were reports of differences among these three viruses in their role in causing Roseola (B, not A), prevalence in various populations, and the possibility of association with some serious human diseases, such as a subset of severe fatigue states, drug induced activation with some organ damage, and most important of all – multiple sclerosis. In regard to the role of HHV-6 in any of these more significant diseases, it appears to me that the problem is not so much a lack of supportive results but the lack of definitive experiments. Such experiments, e.g., clinical trials with virus specific drugs, and/or primate experimental results, are costly, but this is a field that is notoriously underfunded. It is likely it will remain so unless linkage to an important disease (like MS) is definitively established. Consequently, we have a classical dilemma. Money will beget the needed results; needed results will beget the money, but how does the field break the lock? Maybe this will not be possible, but it would be very helpful if greater clarity was established and this begins with appropriate distinctions between these viruses. Some state HHV-6 as ubiquitous. Others state HHV-6B as ubiquitous, but HHV-6A is far less prevalent. First and foremost, there is the need for assays which definitively distinguish A from B, and with such assays to precisely determine the prevalence (and incidence) of infections among different populations. If then there remain convincing major differences in prevalence and in virus association with Roseola, then we need a name change. HHV-6A should then be named HHV-6; HHV-6B becomes HHV-7; and HHV-7 should become HHV-9. Then, we might be able to make specific associations of HHV-6 with other diseases. This would go a long way in alleviating confusion and disinterest by people outside the field. An estimate of the situation at this point in time indicates that there may be important differences between A and B already established to make these name distinctions. Currently the best candidates for serious diseases that might involve HHV-6A as a causative agent are: (1) MS (a subset); (2) other neurological disorders; (3) lymphomas; and (4) contributing to immune dysfunction in people already immune compromised, e.g., as in HIV infection or chemically immune suppressed patients, as in transplant patients. In regards to #4 above, my colleague Paolo Lusso and I have long suggested that HHV-6A may be a factor which accelerates progression to AIDS in HIVH (2) a drug trial. This issue of Journal of Clinical Virology includes a collection of papers by leaders in the field. This will include a report by Paola Lusso, who will describe our results with M. Mulnati and P. Markham in macaques doubly infected with SIV and HHV-6A. These results support the idea that HHV-6A can indeed promote progression to AIDS.