Figure 5.

Some viruses activate HIF-1 by stabilization or increased expression of HIF-1α. The transcription factor HIF-1 is a heterodimer consisting of HIF-1α and the constitutively expressed HIF-1ß. Under normoxic conditions HIF-1α is hydroxylated by prolylhydroxylase (PHD) at conserved proline residues making HIF-1α recognizable for the Von Hippel-Lindau E3 ubiquitin ligase (VHL) complex which leads to rapid degradation by the proteasome. Some viruses are able to inhibit proteasomal degradation of HIF-1α even under normoxic conditions by inhibiting PHD or blocking association of HIF-1α with VHL; others may enhance expression of HIF-α.