The Balagopal Lab has adapted high-resolution tools to study viruses in situ. Specifically, we were the first to quantify hepatitis C virus (HCV) infection in single hepatocytes by developing single-cell laser capture microdissection (scLCM) and integrating this tool with highly sensitive quantitative real-time PCR. We reported that HCV infects a minority of hepatocytes that are found in geospatial clusters. More recently, we (PIs Balagopal and Thio) integrated scLCM with droplet digital PCR (ddPCR) to reveal the first observations of hepatitis B virus (HBV) infection at single cell resolution in the liver. We found that HBV infects nearly all hepatocytes prior to antiviral therapy. However, during antiviral therapy, HBV infection is diminished while viral transcription is markedly attenuated. Our lab has also focused on HIV-1 infection and immune activation for over a decade. Most recently, we have studied type 1 interferon responses to HIV-1 using RNA sequencing (RNAseq). Using this technology, we identified novel interferon-stimulated genes (ISGs) that are associated with HIV-1 restriction in vivo.

Epstein-Barr virus and Kaposi's sarcoma herpesvirus are found in association with a variety of cancers. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to prevent, diagnose or treat them. We have become particularly interested in the unfolded protein response in activation of latent viral infection. Among the notions that we are exploring is the possibility that activation of virus-encoded enzymes will allow the targeted delivery of radation. In addition, we are investigating a variety of virus-related biomarkers including viral DNA, antibody responses, and cytokine measurements that may be clinically relevant.