Increased Serological Response Against Human Herpesvirus 6A Is Associated With Risk for Multiple Sclerosis. Engdahl E, Gustafsson R, Huang J, Biström M, Lima Bomfim I, Stridh P, Khademi M, Brenner N, Butt J, Michel A, Jons D, Hortlund M, Alonso-Magdalena L, Hedström AK, Flamand L, Ihira M, Yoshikawa T, Andersen O, Hillert J, Alfredsson L, Waterboer T, Sundström P, Olsson T, Kockum I, Fogdell-Hahn A. Front Immunol. 2019 Nov 26;10:2715. doi: 10.3389/fimmu.2019.02715.
Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) aetiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS cohort (8,742 people with MS and 7,215 matched controls), and a pre-MS cohort (478 individuals and 476 matched controls) to investigate this further. The IgG response against IE1A was positively associated with MS (OR = 1.55, p = 9 × 10-22), and increased risk of future MS (OR = 2.22, p = 2 × 10-5). An interaction was observed between IE1A and Epstein-Barr virus (EBV) antibody responses for MS risk (attributable proportion = 0.24, p = 6 × 10-6). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10-11). The association did not differ between MS subtypes or vary with severity of disease. The genetic control of HHV-6A/B antibody responses were located to the Human Leukocyte Antigen (HLA) region and the strongest association for IE1A was the DRB1*13:01-DQA1*01:03-DQB1*06:03 haplotype while the main association for IE1B was DRB1*13:02-DQA1*01:02-DQB1*06:04. In conclusion a role for HHV-6A in MS aetiology is supported by an increased serological response against HHV-6A IE1 protein, an interaction with EBV, and an association to HLA genes.
What is the aetiological triggerof MS. Is it EBV, is it something else, is it EBV and something else. HHV6 has been around as a candidate since the 1990s and appears to be more common
Human herpesvirus 6 (HHV-6) is the common collective name for Human betaherpesvirus 6A (HHV-6A) and Human beta herpesvirus 6B (HHV-6B). These closely related viruses are two of the nine herpesviruses known to have humans as their main target and host. HHV-6 has been reported to transactivate EBV. Individuals are at a 10-fold less risk of MS if they are seronegative for EBV. However, among individuals who are positive, those that acquire EBV infection later in life are at a 3-fold greater risk for MS.
77% of humans are exposed to HHV-6B by the age of two and the prevalence of HHV-6 in adults is assumed to be over 90%. After the primary infection, the HHV-6 DNA appears briefly in the serum (and spinal fluid) and then a small amount of virus establishes latency. HHV-6 active infections can persist in the brain tissue long after all traces of the virus have disappeared from the blood,hence the interest in MS.
HHV-6 may activate EBV so both viruses could be involved. This will be a case of if an anti-viral is developed that tackles HHV-6 will it change the risk of developing MS