Latent infection of human herpesvirus 6 in astrocytoma cell line and alteration of cytokine synthesis

In order to study the pathogenesis of HHV-6 infection in central nervous system disorders, U251 cell line was infected with freshly isolated variant B HHV-6. Although IEA/ex 3 antigen (immediate early protein) was detected in infected cell nuclei, neither the presence of OHV-3 antigen (late antigen) nor production of infectious virus was demonstrated. These results indicate that abortive infection was established in the cells. After viral infection, the viral genome copy in the infected cells gradually decreased and became stable after 6 cell passages. At that point, HHV-6 gene expression was restricted to only 2 immediate early genes (U90 and U94). However, 12-O-tetra-decanoyl (TPA) treatment induced transcription of other genes (U31 and U39) by the 10th cell passage, indicating HHV-6 reactivation. Moreover, production of two proinflamatory cytokines (IL-6 and IL-1β) was up-regulated by the presence of the HHV-6 genome and TPA-induced activation of the viral transcripts.