Figure 8.

Working model of the effect of hCMV on EPO production. (A) Under conditions of normal oxygen, HIF2α is constitutively produced, bound to proteasomal degradation by the von Hippel-Lindau tumor suppressor (pVHL), and targeted for degradation. (B) Under conditions of low oxygen, pVHL does not bind to HIF2α, so it is spared from degradation. It can then bind to the β-subunit, translocate to the nucleus, and induce the transcription EPO. (C) Under conditions of normal oxygen, hCMV inhibits the constitutive production of HIF2α, but there is no noticeable effect because the protein is usually degraded. (D) Under conditions of low oxygen, the hCMV-induced inhibition of HIF2α protein production results in being less spared from degradation, reduced binding to the β-subunit, and thus reduced transcription of EPO.