Peter Burbelo from the National Institute of Health has developed a novel HHV-6 serological assay that can differentiate between HHV-6A and HHV-6B. Burbelo used the luciferase immunopreciptiation systems (LIPS) assay for detection, which appears to have great potential for identifying antibodies to pathogens (such as HHV-6) that are difficult to detect in the serum after the acute phase.
The group analyzed hundreds of samples from various populations. As expected HHV-6B seropositivity was found in most healthy blood donors from the US, but HHV-6A was scarce among US samples. On the other hand HHV-6A was found in 48% of samples from Mali in South Africa. Western Africa has a high prevalence of HHV-6A and in that region and the majority of infants develop HHV-6A before HHV-6B infections.
In their study of patients with CFS, the group found no statistical difference in serological positivity for either virus compared to that of controls. Surprisingly, the authors targeted late antibodies (appropriate for an acute reactivation) instead of early/intermediate/latent antibodies that would be produced from the type of persistent/ abortive infection that is suspected in CFS patients. Past studies of both CFS patients that have used assays targeted at abortive infection (by measuring antibodies to the p41 early antigen protein) have been positive for an association. One study found that 77% of CFS patients compared to 12% of controls had antibodies to HHV-6 early antigen antibodies (Patnaik 1995) and another found 57% of CFS patients compared to 16% of controls had IgM antibodies to HHV-6 early antigen (Ablashi 2000). Studies that have looked for HHV-6 late antibodies, on the other hand, have been mixed: five were negative (Burbelo 2012, Chapenko 2012, Buchwald 1996, Wallace 1999, Levine 1992, and Gupta 1991). Similarly in MS studies, serological assays that target intermediate early or early antigen antibodies have been positive for an association with HHV-6 (Ablashi 2000, Soldan 1997, Patnaik 1995, Ben-Fredj 2012) while those using late antibodies have been mixed (Nielsen 1997, Gutierrez 2002, Sola 1993).
Nevertheless, the assay may open the door for increased exploration into the seroepidemiology of HHV-6A and HHV-6B infection. The assay focuses on the detection of differentiated antigens encoded by gene U11 for HHV-6A (p100) and HHV-6B (p101).