Activation of microglia in cortical lobes and possible associations with human herpesvirus 6 and 7 infection

During persistent human beta-herpesvirus (HHV) infection, clinical manifestations may not appear. However, the lifelong influence of HHV is often associated with pathological changes in the central nervous system. Herein, we evaluated possible associations between immunoexpression of HHV-6, -7, and cellular immune response across different brain regions. The study aimed to explore HHV-6, -7 infection within the cortical lobes in cases of unspecified encephalopathy (UEP) and nonpathological conditions. We confirmed the presence of viral DNA by nPCR and viral antigens by immunohistochemistry. Human brain tissue autopsy samples from the frontal and temporal lobes of 24 elderly subjects with UEP and 24 age-matched controls were used in this study. Brain tissue samples were assayed for HHV-6,-7 using nested PCR. Conventional immunohistochemistry using anti-HHV-6, -7 and anti-CD68 antibodies and confocal microscopy was applied. Immunostaining intensity was assessed with an additional quantitative estimation of immunopositive cells. GraphPad Prism 9 program was used for statistical analysis. Overall, we have shown a significant increase (p < 0.001) of HHV antigen expression, especially HHV-7 in the temporal gray matter. Although HHV-infected neurons were found notably in the case of HHV-7, our observations suggest that higher (p < 0.001) cell tropism is associated with glial and endothelial cells in both UEP group and controls. HHV-6, predominantly detected in oligodendrocytes (p < 0.001), and HHV-7, predominantly detected in both astrocytes and oligodendrocytes (p < 0.001), exhibit varying effects on neural homeostasis. This indicates a high number (p < 0.001) of activated microglia observed in the temporal lobe in the UEP group. The question remains of whether human HHV contributes to neurological diseases or are markers for some aspect of the disease process.