Human herpesvirus 6A induces apoptosis of HSB-2 cells via a mitochondrion-related caspase pathway.

Apoptosis plays an important role in the pathogenesis of viral infections. In this study, we investigated the cell death processes during productive HHV-6A infection and the underlying mechanisms. Annexin V-PI staining and electron microscopy indicated that HHV-6A is a strong inducer of apoptosis. HHV-6A infection decreased mitochondrial transmembrane potential and led to morphological changes of mitochondria. The cell death was associated with activation of caspase-3 and cleavage of DNA repair enzyme poly (ADP-ribose) polymerase, which is known to be an important substrate for activated caspase-3. Caspase-9 was activated significantly in HHV-6A-infected cells, whereas caspase-8 was not activated obviously. Moreover, HHV-6A infection upregulated Bax and downregulated Bcl-2. This is the first demonstration of mitochondrion-mediated, caspase-dependent apoptosis in HHV-6A-infected cells.