FIG 10.

Proposed model for HCMV regulation of autophagy and survival. Upon entering circulation from the bone marrow, peripheral blood monocytes undergo apoptosis within 48 h in the absence of myeloid differentiation factors. In addition to the intrinsic proapoptotic programing of monocytes, HCMV infection triggers host antiviral self-death pathways resulting in an exceedingly proapoptotic environment within the infected cell. To circumvent apoptosis, HCMV induces the rapid upregulation of several cellular prosurvival proteins that leads to a persistent inactivation of caspase 8 (31, 32, 41, 43, 44). Consequently, necroptosis is triggered as a “trap door” mechanism of cell death within infected monocytes. However, the concomitant activation of AMPK by HCMV leads to the upregulation of autophagosomal production and maturation that then blocks necroptotic cell death prior to MLKL activation.