Arash Grakoui

Summary

Affiliation: Emory University
Country: USA

Publications

  1. pmc Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness
    Luke Uebelhoer
    Department of Medicine, Division of Infectious Diseases, Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS Pathog 4:e1000143. 2008
  2. pmc Impaired hepatitis C virus (HCV)-specific effector CD8+ T cells undergo massive apoptosis in the peripheral blood during acute HCV infection and in the liver during the chronic phase of infection
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road, NE, Atlanta, GA 30329, USA
    J Virol 82:9808-22. 2008
  3. pmc Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road N E, Atlanta, GA 30329, USA
    J Virol 81:2545-53. 2007
  4. pmc Transient CD86 expression on hepatitis C virus-specific CD8+ T cells in acute infection is linked to sufficient IL-2 signaling
    Henry Radziewicz
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    J Immunol 184:2410-22. 2010
  5. pmc Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity
    Brian A Norris
    Vaccine Research Center, Emory University, Atlanta, GA 30329, USA
    Immunity 38:309-21. 2013
  6. pmc Differential expression of CD26 on virus-specific CD8(+) T cells during active, latent and resolved infection
    Chris C Ibegbu
    Emory Vaccine Center and Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    Immunology 126:346-53. 2009
  7. ncbi request reprint Memory CD8+ T cell differentiation in viral infection: a cell for all seasons
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road, NE, Atlanta, GA 30329, United States
    World J Gastroenterol 13:4848-57. 2007
  8. pmc Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death
    Guaniri Mateu
    Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA
    Virology 376:397-407. 2008
  9. pmc Hepatic enrichment and activation of myeloid dendritic cells during chronic hepatitis C virus infection
    Victoria M Velazquez
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    Hepatology 56:2071-81. 2012
  10. pmc Hepatic stellate cells preferentially induce Foxp3+ regulatory T cells by production of retinoic acid
    Richard M Dunham
    Division of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 190:2009-16. 2013

Research Grants

Collaborators

Detail Information

Publications24

  1. pmc Stable cytotoxic T cell escape mutation in hepatitis C virus is linked to maintenance of viral fitness
    Luke Uebelhoer
    Department of Medicine, Division of Infectious Diseases, Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America
    PLoS Pathog 4:e1000143. 2008
    ..These studies suggest that HCV escape mutants emerging early in infection are not necessarily stable, but are eventually replaced with variants that achieve a balance between immune evasion and fitness for replication...
  2. pmc Impaired hepatitis C virus (HCV)-specific effector CD8+ T cells undergo massive apoptosis in the peripheral blood during acute HCV infection and in the liver during the chronic phase of infection
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road, NE, Atlanta, GA 30329, USA
    J Virol 82:9808-22. 2008
    ..This study highlights the importance of cytokine deprivation-mediated apoptosis with consequent down-modulation of the immune response to HCV during acute and chronic infections...
  3. pmc Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road N E, Atlanta, GA 30329, USA
    J Virol 81:2545-53. 2007
    ....
  4. pmc Transient CD86 expression on hepatitis C virus-specific CD8+ T cells in acute infection is linked to sufficient IL-2 signaling
    Henry Radziewicz
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    J Immunol 184:2410-22. 2010
    ..Expression of costimulatory molecules, such as CD86, early in HCV infection may be essential in overcoming inhibitory signals from the high level of programmed death receptor 1 expression also seen at this phase of infection...
  5. pmc Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity
    Brian A Norris
    Vaccine Research Center, Emory University, Atlanta, GA 30329, USA
    Immunity 38:309-21. 2013
    ..The reduction of monocytic cells in Ccr2(-/-) mice or after Gr-1 antibody depletion enhanced antiviral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection...
  6. pmc Differential expression of CD26 on virus-specific CD8(+) T cells during active, latent and resolved infection
    Chris C Ibegbu
    Emory Vaccine Center and Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    Immunology 126:346-53. 2009
    ..This marker has the potential to be useful in studies of immune responses to infectious agents, and to new vaccine candidates...
  7. ncbi request reprint Memory CD8+ T cell differentiation in viral infection: a cell for all seasons
    Henry Radziewicz
    Emory University School of Medicine, 954 Gatewood Road, NE, Atlanta, GA 30329, United States
    World J Gastroenterol 13:4848-57. 2007
    ..A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system...
  8. pmc Intragenotypic JFH1 based recombinant hepatitis C virus produces high levels of infectious particles but causes increased cell death
    Guaniri Mateu
    Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA 30329, USA
    Virology 376:397-407. 2008
    ..These studies begin to unravel requirements for robust virus replication and the relationship between increased virion production and host cell viability...
  9. pmc Hepatic enrichment and activation of myeloid dendritic cells during chronic hepatitis C virus infection
    Victoria M Velazquez
    Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    Hepatology 56:2071-81. 2012
    ..Importantly, pDC and mDCs from HCV-infected liver were capable of secreting effector cytokines, interferon-alpha and interleukin-12, respectively, in response to Toll-like receptor stimulation in vitro...
  10. pmc Hepatic stellate cells preferentially induce Foxp3+ regulatory T cells by production of retinoic acid
    Richard M Dunham
    Division of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 190:2009-16. 2013
    ..Thus, we conclude that HSCs preferentially generate Foxp3(+) Tregs and, therefore, may play a role in the tolerogenic nature of the liver...
  11. pmc Hepatitis C virus is primed by CD81 protein for low pH-dependent fusion
    Nishi R Sharma
    Division of Pediatric Infectious Diseases, Emory University Children s Center, Atlanta, Georgia 30322, USA
    J Biol Chem 286:30361-76. 2011
    ..The simple triggering paradigm and intermediate conformations of E1E2 identified in this study could help guide future vaccine and therapeutic efforts to block HCV infection...
  12. pmc PD-1 tempers Tregs in chronic HCV infection
    Henry Radziewicz
    Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329, USA
    J Clin Invest 119:450-3. 2009
    ....
  13. pmc B7-H4 mediates inhibition of T cell responses by activated murine hepatic stellate cells
    Raghavan Chinnadurai
    Department of Medicine, Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30329, USA
    Hepatology 52:2177-85. 2010
    ....
  14. pmc Glucagon-like peptide-1 receptor is present on human hepatocytes and has a direct role in decreasing hepatic steatosis in vitro by modulating elements of the insulin signaling pathway
    Nitika Arora Gupta
    Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA
    Hepatology 51:1584-92. 2010
    ..Small interfering RNA against GLP-1R abolished the effects on PDK-1 and PKC-zeta. Treatment with exendin-4 quantitatively reduced triglyceride stores compared with control-treated cells...
  15. ncbi request reprint Unraveling the role of PD-1/PD-L interactions in persistent hepatotropic infections: potential for therapeutic application?
    Henry Radziewicz
    Gastroenterology 134:2168-71. 2008
  16. pmc Memory CD8+ T cells are required for protection from persistent hepatitis C virus infection
    Naglaa H Shoukry
    Center for Vaccines and Immunity, Columbus Children s Research Institute, Columbus, OH 43205, USA
    J Exp Med 197:1645-55. 2003
    ..These experiments demonstrate an essential role for memory CD8+ T cells in long-term protection from chronic hepatitis C...
  17. ncbi request reprint HCV persistence and immune evasion in the absence of memory T cell help
    Arash Grakoui
    Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA
    Science 302:659-62. 2003
    ....
  18. ncbi request reprint Characterization of HCV-specific Patr class II restricted CD4+ T cell responses in an acutely infected chimpanzee
    David J Woollard
    Center for Vaccines and Immunity, Columbus Children s Research Institute, Columbus, OH 43205, USA
    Hepatology 38:1297-306. 2003
    ..In conclusion, the characterization of the HCV epitopes and MHC class II restriction elements described here will facilitate a detailed comparison of CD4+ T cell function in animals with resolved and persistent infections...
  19. pmc Lack of phenotypic and functional impairment in dendritic cells from chimpanzees chronically infected with hepatitis C virus
    Marie Larsson
    New York University School of Medicine, New York, NY 10016, USA
    J Virol 78:6151-61. 2004
    ....
  20. pmc Variable patterns of programmed death-1 expression on fully functional memory T cells after spontaneous resolution of hepatitis C virus infection
    David G Bowen
    Center for Vaccines and Immunity, The Research Institute at Nationwide Children s Hospital, 700 Childrens Dr, Columbus, OH 43205, USA
    J Virol 82:5109-14. 2008
    ..This animal model should facilitate studies of whether PD-1 differentially influences effector and memory T-cell function in resolved versus persistent human infections...
  21. ncbi request reprint Turning on the off switch: regulation of anti-viral T cell responses in the liver by the PD-1/PD-L1 pathway
    Arash Grakoui
    J Hepatol 45:468-72. 2006
  22. ncbi request reprint Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics
    Tobias Marcello
    Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10021, USA
    Gastroenterology 131:1887-98. 2006
    ..We aimed to determine whether IFN-lambda exhibits antiviral activity toward HCV and to compare the signal transduction and effector gene pathways with those of IFN-alpha...
  23. pmc Evidence for a functional RNA element in the hepatitis C virus core gene
    Laura K McMullan
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 104:2879-84. 2007
    ..We conclude that ARF-encoded proteins initiating at the polyprotein AUG are not essential for HCV replication in cell culture or in vivo. Rather, our results provide evidence for a functionally important RNA element in the ARF region...
  24. pmc Clearance of replicating hepatitis C virus replicon RNAs in cell culture by small interfering RNAs
    Glenn Randall
    Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 100:235-40. 2003
    ..The introduction of siRNAs into cells with established HCV replication cured >98% of these cells of detectable HCV antigen and replication-competent HCV RNAs. These data support the principle of siRNA-based HCV antiviral therapy...

Research Grants6

  1. Mechanisms of hepatitis C virus persistence
    Arash Grakoui; Fiscal Year: 2010
    ..The work proposed here is based both on our work in the chimpanzee model and on observations in human patients. The experimental focus of this proposal is on defining the mechanisms by which T cells fail in persistent HCV infection. ..
  2. Mechanisms of hepatitis C virus persistence
    Arash Grakoui; Fiscal Year: 2007
    ..The work proposed here is based both on our work in the chimpanzee model and on observations in human patients. The experimental focus of this proposal is on defining the mechanisms by which T cells fail in persistent HCV infection. ..
  3. Defining the intrahepatic immune response to hepatitis C virus
    Arash Grakoui; Fiscal Year: 2010
    ..We are seeking to elucidate and understand the mechanisms by which the host immune response fails in the majority of those infected and to future efforts to develop prophylactic and/or therapeutic HCV eradication strategies. ..