Mathematical Modeling of Protracted HCMV Replication using Genome Substrates and Protein Temporal Profiles

• DOI: 10.1096/fasebj.2022.36.s1.r6216
• Publication Date: 2022-05-03T08:23:48Z
• Authors: Christopher E. Monti; Rebekah Mokry; Megan Schumacher; Ranjan Dash; Scott Terhune
• Keywords: Lytic cycle; Replication

Clinical manifestations of human cytomegalovirus (HCMV) infection, a major cause morbidity and mortality in the immunocompromised, are associated with lytic replication cycle. Lytic occurs over 96 hrs is marked by viral DNA (vDNA) synthesis expression proteins, latter which can be generalized into distinct temporal classifications. Given complexity cycle, mathematical modeling used to probe this elaborate system. Recently, has been study early cycle transition between latent cycles. To date, there appears few studies focusing on late phases cycle.vDNA kinetics were probed using qPCR assays absolute quantification varying multiplicities infection (MOIs) fibroblasts. An empiric model vDNA was generated parameterized these data then compared obtained post hoc. The drive that incorporated protein class culminated virion production. This from immunoblots representative proteins profile titering at three different MOIs. Predictions hoc high-temporal-resolution, fluorescence-based concentration measurements one 96-hr cycle.A MOI-dependent developed experimental data. mechanistic. It predicts feedback inhibition production an increase degradation following vDNA. Both models yielded 3 primary predictions: (1) presence saturation high MOIs, (2) inefficient low (3) range MOIs virus maximized. Saturation likely represents physical limitations cellular machinery. Inefficient indicates minimum MOI required sustain infection. Identification maximal set conditions most favorable HCMV where extraneous material minimized, while both number cells amount delivered each cell maximized.A occurs, extended predict dynamics during