Tracking Real-time Viral Infection of Living Tissue with Holographic Dynamic-Contrast OCT

Pandemics have been present throughout human history. Although antibiotics and vaccines have aided in lowering death tolls, new outbreaks of novel pathogens, like COVID-19, cause severe outbreaks that increase mortality rates, disrupting global health systems and socioeconomic stability. Development of antiviral therapeutics and viral detection assays have aided in treating and identifying viral infections. However, there is a lack of fast in-vitro assays for testing antiviral efficacy in individual patients. As a first step to address this gap, this work uses biodynamic imaging (BDI), a holographic dynamic-contrast OCT method, to track viral infection of 3-dimensional cell cultures in a longitudinal assay. BDI has been used previously as an assay for testing chemotherapeutic drug efficacy from patient tissue as well as being used for antibiotic assays. To apply BDI to viral tracking, we use Adenovirus 6 (AV6) to infect 3D adenocarcinoma cells (DLD1) and track changes in intracellular motion over time in response to infection. AV6 induces changes in cellular and nuclear membranes, and a similar response is seen in BDI Doppler signatures. Enhancement of motion in the nuclear and cellular membranes is seen up to 20 hours post infection, at which time cell health degrades due to the advancement of cytopathic effects caused by viral infection. These results serve as a first step in studying the effects that viruses induce on intracellular motion and serve as a baseline for developing antiviral assays.