Mentor: Jack Stapleton, M.D.
Lab Room: Bldg. 40, Room 104 VAMC
Lab Phone: 319-338-0581

Effects of GBV-C infection on T cell activation and IL-2 signaling pathways

Human immunodeficiency virus (HIV) infection and HIV mediated acquired immunodeficiency syndrome (AIDS) remain a major global public health crisis. Chronic HIV infection and AIDS progression are associated with increased T cell activation. Lower CD4+ T cell gain in HIV-infected individuals under antiretroviral therapy (ART) is also associated with higher T cell activation suggesting therapies that lower immune activation may benefit these individuals. Persistent infection with a flavivirus GB virus C (GBV-C) is associated with prolonged survival of HIV-1 infected individuals, lower surface expression of T cell activation markers and impaired response to IL-2 therapy suggesting GBV-C infection modulates T cell activation and/or proliferation. Currently our work is focused on elucidating mechanisms by which GBV-C alters T cell activation pathways. Our hypothesis is GBV-C modulates T cell activation and IL-2 signaling pathways, and that this effect is mediated at least in part by the envelope glycoprotein E2. Understanding mechanism(s) by which GBV-C alters T cell activation might provide insights into GBV-C/ HIV interaction and novel therapies to treat HIV.

Publications:

McLinden JH, Stapleton JT, Klinzman D, Murthy KK, Chang Q, Kaufman TM, Bhattarai N, Xiang J. Chimpanzee GB virus C and GB virus A E2 envelope glycoproteins contain a peptide motif that inhibits HIV-1 replication in human CD4+ T cells. J Gen Virol. 2013 Jan 3. [Epub ahead of print] PubMed PMID:23288422

Rydze RT, Bhattarai N, Stapleton JT. GB virus C infection is associated with a reduced rate of reactivation of latent HIV and protection against activation-induced T-cell death. Antivir Ther. 2012 Sep 5. doi: 10.3851/IMP2309. [Epub ahead of print] PubMed PMID: 22951385.

Bhattarai N, Rydze RT, Chivero ET, Stapleton JT. GB Virus C Viremia Is Associated With Higher Levels of Double-Negative T Cells and Lower T-Cell Activation in HIV-Infected Individuals Receiving Antiretroviral Therapy. J Infect Dis. 2012 Sep 12. [Epub ahead of print] PubMed PMID: 22927453.

Bhattarai N, McLinden JH, Xiang J, Kaufman TM, Stapleton JT. GB Virus C Envelope Protein E2 Inhibits TCR-Induced IL-2 Production and Alters IL-2-Signaling Pathways. J Immunol. 2012 Sep 1;189(5):2211-6. Epub 2012 Jul 27. PubMed PMID: 22844114; PubMed Central PMCID: PMC3424397.

Bhattarai N, Stapleton JT. Study design may explain discrepancies in GB virus C effects on interferon-γ and interleukin-2 production and CD38 expression in T lymphocytes. Mem Inst Oswaldo Cruz. 2012 Jun;107(4):568-9; author reply 569. PubMed PMID: 22666874.

Xiang J, McLinden JH, Kaufman TM, Mohr EL, Bhattarai N, Chang Q, Stapleton JT. Characterization of a peptide domain within the GB virus C envelope glycoprotein (E2) that inhibits HIV replication. Virology. 2012 Aug 15;430(1):53-62. Epub 2012 May 16. PubMed PMID: 22608061.

Bhattarai N, Stapleton JT. GB virus C: the good boy virus? Trends Microbiol. 2012 Mar;20(3):124-30. Epub 2012 Feb 8. Review. PubMed PMID: 22325031.

Abstracts:

Bhattarai N, Rydze RT, Xiang J, Landay AL, McLinden JH, Stapleton JT. GBV-C infection effects on T cell activation and IL-2 secretion can be mediated by the envelope glycoprotein E2. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Rome, Italy, 2011.

Rydze RT, Bhattarai N, Wallace W, Stapleton JT. GBV-C infection reduces reactivation of latent HIV and decreases PBMC proliferation in vitro. 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Rome, Italy, 2011.