Cellular Determinants of HCMV infection

Human Cytomegalovirus (HCMV) causes substantial disease in immunosuppressed patients, including hematological cancer patients and transplant recipients. Further, HCMV is a major cause of congenital disability. Successful HCMV infection relies on the viral modulation of many cellular factors. To identify novel cellular determinants of HCMV infection, we have performed targeted CRISPR screens of biochemical data sets and identified JUNB as a cellular factor that can inhibit HCMV infection. JUNB is a stress-induced transcription factor that regulates inflammation. Our data suggests that the HCMV UL26 protein binds JUNB, thereby attenuating its anti-viral activity. We will identify the mechanisms through which JUNB can restrict HCMV infection (Aim 1) and elucidate how JUNB induces the activation of inflammatory gene expression (Aim 2). Lastly, we will determine how UL26 modulates JUNB’s activity (Aim 3). Collectively, our proposed research will explore how a key inhibitor of anti-viral responses, UL26, modulates the activity of an important regulator of inflammation, JUNB. The mechanisms involved will further our understanding of important host-pathogen interactions and could potentially pave the way for novel therapeutic interventions.