Synthesis of mitochondrial macromolecules in herpes simplex type 1 virus infected Vero cells

Abstract

How viral infections affect host cell mitochondrial functions is largely unknown. In this study, uptake of radiolabeled precursors was used to assess how a herpes simplex virus type 1 (HSV 1) infection influences synthesis of macromolecules comprising Vero cell mitochondria. Total macromolecular synthesis in infected cells was determined for comparative purposes. Mitochondrial and total cellular DNA syntheses were approximately halved at 1–2.5 h postinfection (PI). Mitochondrial DNA synthesis in infected cells then rose to 3.5-fold that in control cells at 3–4.5 h PI. Total DNA synthesis in infected cells also rose, but more slowly, reaching threefold that for control cells at 5–6.5 h PI. Mitochondrial and total RNA synthesis in infected cells were both decreased by approximately 40% at 1–3 h PI. Over the next 4 h, total RNA synthesis in infected cells slowly continued to decrease, while that in mitochondria recovered to control levels. Synthesis of mitochondrial proteins in infected cells decreased progressively, dropping to about 60% of control levels by 5–6.5 h PI. With the metabolic inhibitors ethidium bromide and cycloheximide, it was determined that nuclear DNA and mitochondrial DNA directed synthesis of mitochondrial proteins were each partially inhibited in infected cells. Total cellular protein synthesis was decreased by 30% at 1–2.5 h PI and then recovered to control levels by 5–6.5 h PI. Finally, phospholipid synthesis in mitochondria from infected cells was elevated 2.3–fold at 1–5 h PI, but dropped to 14% below control levels during 4–8 h PI. Total phospholipid synthesis in infected cells was up 12% and down 11%, respectively, for the same two time periods. These results show that synthesis of each class of mitochondrial macromolecules is uniquely altered in cells infected by HSV 1.