Faculty Summaries
John M. Taylor, PhD
John M. Taylor, PhD
Professor Emeritus
  • Adjunct Associate Professor of Microbiology, University of Pennsylvania, Philadelphia, PA
John.Taylor@fccc.edu
Office Phone: Phone: 215-728-2436
Lab Phone: 215-728-2432
Office: R295
  • Overview of Research Interests

    We study two viruses that can infect the human liver. These are known as hepatitis B virus (HBV) and hepatitis delta virus (HDV). Chronic infections can lead to extensive liver damage and a greatly increased risk of proceeding to cancer. One current research interest is to understand how these two viruses are able to enter cells into liver cells. The second, more long-term research interest, is to understand how the HDV is able to replicate its ribonucleic acid (RNA) genome.

  • Mechanism(s) of Virus Attachment and Entry

    HBV and HDV in nature only infect the hepatocytes of the liver. Experimental attempts to infect cultured cells with these viruses have been essentially limited to the use to primary hepatocytes. HDV uses the envelope proteins of HBV for its own assembly and also for the attachment and entry into primary hepatocytes. We are attempting to understand the mechanism(s) involved. As part of this study we have constructed lentivirus pseudotypes that contain HBV envelope proteins. These pseudotypes, like HBV and HDV, have the same host cell specificity and seem to use the same region on one of the HBV envelope proteins as a ligand for specific attachment to the host cell. However, in the subsequent steps of entry the three viruses differ. HBV and HDV are sensitive to inhibitors of endocytosis and of acidification in endosomal compartments. The pseudotype is not sensitive and may enter via direct fusion at the plasma membrane.

    Top
  • Initiation of HDV RNA-Directed RNA Transcription

    The genome of HDV is a small circular RNA species. Somehow this HDV RNA is able to redirect one or more host RNA polymerases to carry out RNA-directed RNA transcription. We have previously obtained evidence that the host RNA polymerase II is essential for this, although it remains possible that another host polymerase might also participate. We are currently using nuclear run-on and affinity selection procedures to isolate and characterize nascent HDV RNA transcripts. In this way we will determine the sites of initiation and thence determine the sequence and structural features on HDV RNAs that allow them to act as templated for such redirected RNA transcription.

    Top
  • The Pathogenic Effects of HDV Replication
    Host mRNAs changes caused by HDV
    Host mRNAs changes caused by HDV

    Patients infected with both HDV and HBV have more damaging liver damage than those infected with only HBV. We are using cell systems to understand what changes in host mRNA transcription are produced by HDV genome replication. Using array technology to assay for 22,000 human mRNA we have shown that HDV replication causes 900 host mRNA to be changed by at least 2-fold. Already this has explained that HDV replication can produce a cell cycle arrest. At the same time, HDV like HBV, does not induce genes considered to be part of the host innate immune response. We have found that HDV replication can actually suppress the induction of this response by poly(IC). In addition, if the innate response is first activated by poly(IC), this will suppress the HDV replication.

    Top