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.

The Clinical Laboratory and Biomarkers Cores will coordinate access to laboratory expertise, testing, training, specimen repositories and Good Clinical Laboratory Practices (GCLP). The goals of this core are to assure that all JHU HIV investigators have access to and utilize appropriate, validated and, where applicable, certified laboratory assays. The core will also maintain a biomarker specimen repository for storage cataloguing and utilization of biological specimens.

Research in the Andrea Cox Lab explores the immune response in chronic viral infections, with a focus on HIV and the hepatitis C virus (HCV). In our studies, we examine the role of the immune response upon exposure to HCV by examining responses to HCV in a longitudinal, prospective group of high-risk individuals. This enables us to compare the innate, humoral and cellular immune responses to infection with clearance versus persistence. Through our findings, we seek to identify mechanisms of protective immunity against HCV infection and improve HCV vaccine design.

Research in the Retrovirus Laboratory focuses on the molecular virology and pathogenesis of lentivirus infections. In particular, we study the simian immunodeficiency virus (SIV) to determine the molecular basis for the development of HIV CNS, pulmonary and cardiac disease. Research projects include studies of viral molecular genetics and host cell genes and proteins involved in the pathogenesis of disease. We are also interested in studies of lentivirus replication in macrophages and astrocytes and their role in the development of disease. These studies have led us to identify the viral genes that are important in neurovirulence of SIV and the development of CNS disease including NEF and the TM portion of ENV. The mechanisms of the action of these proteins in the CNS are complex and are under investigation. We have also developed a rapid, consistent SIV/macaque model in which we can test the ability of various antiviral and neuroprotective agents to reduce the severity of CNS and pulmonary disease.

Research in the Chloe Thio lab focuses on several areas. First, HBV virology and immunology in HBV monoinfected and HIV-HBV co-infected individuals that will ultimately help develop a cure for HBV. Second, HCV infection in men who have sex with men. Third, non-alcoholic fatty liver disease with a focus on HIV-infected individuals. Fourth, host genetic determinants of spontaneous HBV recovery and HCV clearance.