HHV-6 DNA is not elevated in lupus patients but may have a role in reactivating EBV.
Past studies have found an association between reactivation of EBV and systemic lupus erythematosus (lupus). However, it has been unclear if EBV helps initiate the disease or to produce disease flares, or whether it is an epiphenomenon resulting from the immune dysregulation seen in lupus. Investigators in China studied EBV DNA as well as the mRNA of several lytic and latent EBV genes. They also examined the possibility that HHV-6 might transactivate EBV and thereby serve as apossible “co-acceleration” in lupus patients.
A group of 105 people with lupus (about half in an active stage and half in a stable stage of the disease) were compared to 110 matched healthy control subjects. The former group was significantly more likely to have elevated levels of EBV DNA in peripheral mononuclear cells and to have elevated levels of IgM antibodies to EBV viral capsid antigen. As shown in Figure 1, the same was not true of DNA for HHV-6A/B. Patients with lupus also were much more likely to have detectable expression of EBV genes, although there was no significant difference in EBV gene expression patterns between lupus patients in the active vs. stable phases of the disease.
Figure 1: Elevated levels of EBV DNA and HHV-6A/B DNA in people with lupus and in matched healthy control subjects.
A significant association was found between the expression of the BcLF1 gene of EBV and the detection of elevated levels of HHV-6A/B DNA, raising the possibility that BcLF1 may play a role in transactivating HHV-6. Similarly, the authors speculate that HHV-6 could transactivate EBV in B cells, increasing the expression of EBV immediate early antigen Zebra and early antigen (EA-D and EA-R) by up to ten-fold, as demonstrated by Flamand et al.
This article adds to past evidence of an association between EBV and lupus, but does not resolve the central question of whether the reactivation of EBV seen in both active and stable stages of the disease is a cause or an epiphenomenal effect of the disease. The authors call for further study on the possibility of a synergistic effect of HHV-6 and EBV that might lead to the activation of polyclonal B lymphocytes and abnormal Immune function.
Read the full article: Chen 2023