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. 2020 Apr 6;16(4):e1007733. doi: 10.1371/journal.pcbi.1007733

Fig 9. A mitotic collapse resulting in sustained MPF activity during human cytomegalovirus infection requires APC/C subunit degradation.

Fig 9

Diagrams depicting the mechanisms of (A) HCMV pUL21a suppression of CCNB1 levels, (B) HCMV kinase pUL97 phosphorylation of CDH1, and (C) pUL21-mediated disruption of the APC/C complex during infection. (D) Simulated decrease in CCNB1 (ks1) results in mitotic collapse defined by elevated levels of APC/CT and PTTG1T and loss of MPF (CCNB1:CDK1) and LMNAP. (E) Simulated increase in CDH1P (k′r11) induces a collapse with elevated APC/CT yet loss of MPF, PTTG1, CCNB1 and LMNAP. (F) Increasing degradation of APC/C (kd15.1) results in sustained MPF, LMNAP, and PTTG1T levels. (G) Simulating ranges of pUL21a and/or pUL97 activities in altering LMNAP levels at a single time point of 96 hr. Combined simulated increase in APC/C degradation (kd15.1) with reduced CCNB1 synthesis (ks1) result in low sustained levels of MPF and LMNAP which have been experimentally demonstrated to be required for virus replication and are the target of an antiviral agent. (H) Simulating ranges of pUL21a and pUL97 activities against CCNB1, APC/C and CDH1 and their impact on the levels of LMNAP as indicated by colored scale. Relative concentrations of LMNAP >0.3 are shown.