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

Abstract

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-1beta) was up-regulated by the presence of the HHV-6 genome and TPA-induced activation of the viral transcripts.

Human Herpesvirus 6 (HHV-6) Induces Dysregulation of Glutamate Uptake and Transporter Expression in Astrocytes

“…Primary human astrocytes derived from a single brain are difficult to propogate in large quantities and grow slowly, and insufficient quantities are available to extensively investigate. As a result, we utilized the established model system of GFAP-positive U251 glioma cells that has been used to study HHV-6 (Akhyani et al 2006;Yoshikawa et al 2002) to confirm that the characteristics of HHV-6 infection and dysregulation of glutamate would mimic our observations in primary astrocytes.…”

Sensitivity of human herpesvirus 6 and other human herpesviruses to the broad-spectrum antiinfective drug artesunate

“…2B, lanes 3 and 5) similar to reactivation effects previously reported by others. 23 Initial results of Western blot analyses also suggest an inhibitory effect of ART on HHV-6B (strain Z29) early/late protein synthesis (data not shown).…”

Elevated serum cytokine levels are associated with human herpesvirus 6 reactivation in hematopoietic stem cell transplantation recipients

“…39,40 Although IL-6 synthesis does not increase in HHV-6-infected PBMCs, 39 we observed the enhanced production of this cytokine in a virally infected neuroglial cell line. 41 Furthermore, elevated IL-6 levels have been observed in HHV-6-infected patients that exhibit frequent seizures. 42 Recent microarray analyses have demonstrated that the transcription of mRNA encoding inflammatory cytokines was upregulated in virally infected cells.…”