Jack Stapleton, MD

Internal Medicine

Office: SW54-15 GH
Office Phone: 319-356-3168

Lab: Bldg. 40, RM104 VAMC
319-338-0581, ext. 7586

Our laboratory carries out basic and translational research on GB virus C and hepatitis C virus, and also study these viruses for their interactions with HIV

Our laboratory research is focused on GB virus C (GBV-C), hepatitis C virus (HCV) and other flaviviruses replication, host response and interactions with HIV. We also collaborate with clinical cohorts to study the effects of these virsuses on disease progression of HIV and other diseases. In several epidemiological studies we conducted with University of Iowa HIV patients, and in collaboration with national and international HIV-infected cohorts, we desmontrated that GBV-C is associated with prolonged survival, improved response to HIV therapy, and decreased maternal-fetal transmission of HIV. In the laboratory, we learned that GBV-C is a lymphotropic virus, replicating in B and T lymphocytes, and demonstrated that virus inhibits HIV replication in an in vitro, co-infection model. Current studies are focused on understanding the mechanism(s) by which GBV-C inhibits HIV replication. Studies in our laboratory and others suggest that the envelope glycoprotein (E2) stimulates cells to release chemokines that are known inhibitors of HIV replication, and GBV-C E2 protein appears to decrease the expression of the HIV co-receptor CCR5. Current studies are underway to identify the GBV-C E2 cell receptor, and to identify binding and entry mechanisms for GBV-C and HCV. Another project in the laboratory involves the study of flavivirus non-structural phosphoproteins (NS5). Expression of the GBV-C NS5A protein renders CD4+ T cell lines resistant to HIV replication, and the functional region required has been mapped to a 30 amino acid region. Current structural analysis and mutational analysis of this peptide, and comparative studies of GBV-C and HCV NS5A proteins with other flavivirus NS5 proteins are underway. Our laboratory work is carried out by a team of investigators including Drs. Jinhua Xiang and James McLinden.

PubMed link

Department/Program Affiliations:
Internal Medicine
Molecular Medicine