Multiple receptor tyrosine kinases regulate dengue infection of hepatocytes.

Introduction: Dengue is an arboviral disease causing severe illness in over 500,000 people each year. Currently, there is no way to constrain dengue in the clinic. Host kinase regulators of dengue virus (DENV) infection have the potential to be disrupted by existing therapeutics to prevent infection and/or disease progression.

Host kinase regulation of dormant and replicating liver stages.

Upon transmission to the liver, parasites form replicating schizonts, which continue to initiate blood-stage infection, or dormant hypnozoites that reactivate weeks to months after initial infection. phenotypes in the field vary significantly, including the ratio of schizonts to hypnozoites formed and the frequency and timing of relapse. Evidence suggests that both parasite genetics and environmental factors underly this heterogeneity.

Elucidating Spatially-Resolved Changes in Host Signaling During Liver-Stage Infection.

Upon transmission to the human host, sporozoites exit the skin, are taken up by the blood stream, and then travel to the liver where they infect and significantly modify a single hepatocyte. Low infection rates within the liver have made proteomic studies of infected hepatocytes challenging, particularly , and existing studies have been largely unable to consider how protein and phosphoprotein differences are altered at different spatial locations within the heterogeneous liver. Using digital spatial profiling, we characterized changes in host signaling during infection without disrupting the liver tissue.