Co-induction of apoptotic and necrotic viral cytopathology
Description
Ultrastructural and biochemical data suggest that apoptosis and necrosis are integrally linked in cells infected by cytopathic viruses. In cells lytically infected by HIV or Sindbis virus, apoptosis has been hypothesized to account for the majority of cytopathology. Using quantitative video imaging and DNA fragmentation techniques, DNA fragmentation and necrotic morphology were extensive, however only about 10% of infected cells by various strains were apoptotic. The presence of distended endoplasmic reticulum and swollen or collapsed mitochondria, and abnormal lysosomes were seen in both necrotic and apoptotic cells. Cells simultaneously displaying necrotic morphology and classic apoptotic nuclear morphology were observed. Similar changes were observed in cells treated with the lytic peptide LLP-1. Mitochondrial transmembrane potential is dissipated and host cell pH is altered in all three of these cell populations. These classic 'lytic' systems insult the cell, particularly affecting the mitochondria, and initiate lytic, or necrotic, death that also triggers an apoptotic pathway. This type of induced cell death could release cellular constituents with unique antigenic properties that would not normally be exposed to the immune system. This has important implications for understanding viral pathogenesis and autoimmunity