Contents - College of Medical and Dental Sciences - University of ...

More documents

Recommendations

Info

The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK Immunology I Abstract 11 UPREGULATION OF THE TLR3 PATHWAY BY KSHV DURING PRIMARY INFECTION OF MONOCYTES John West, Sean Gregory and Blossom Damania Department of Microbiology and Immunology and Lineberger Cancer Center, University of North Carolina at Chapel Hill, North Carolina 27599 Abstract Kaposi’s sarcoma-associated herpesvirus (KSHV) is associated with several different human malignancies including Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV establishes lifelong latency in the host and modulates the host immune response. Innate immunity is critical for controlling de novo viral infection. Toll like receptors (TLRs) are key components of the innate immune system and they serve as pathogen recognition receptors that stimulate the host antiviral response. In particular, TLR3 has been implicated in RNA virus recognition. Currently there is no information on how KSHV infection modulates any TLR pathway. We report the first evidence showing that KSHV upregulates TLR3 expression in human monocytes sixteen hours post-infection. This is also the first demonstration of a human DNA tumor virus upregulating TLR3, a TLR that thus far has been associated with the recognition of RNA viruses. We found that KSHV upregulates the TLR3 pathway and induces TLR3-specific cytokines and chemokines, including IFN-β1 and CXCL10 (IP-10). SiRNAs directed against TLR3 greatly reduced the ability of KSHV to upregulate IFN-β1 and CXCL10 upon infection. TLR3 upregulation was monitored at different time-points post-infection. We found that TLR3 expression levels were highest 16 hours postinfection and slowly declined thereafter returning to baseline by 120 hours post-infection as the virus established latency. Presenting author Email: john_west@med.unc.edu 32
The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK Immunology I Abstract 12 KSHV EVADES INNATE IMMUNITY BY SUPPRESSION OF TLR4 EXPRESSION Dimitris Lagos 1 , Richard James Vart 1 , Fiona Gratrix 1 , Samantha Jane Westrop 2 , Ping-Pui Wong 1 , Nesrina Imami 2 , Mark Bower 3 , Frances Gotch 2 and Chris Boshoff 1 1 Cancer Research UK Viral Oncology Group, UCL Cancer Institute, Paul O’Gorman Building, Huntley Street, University College London, WC1E 6BT, London, U.K. 2 Department of Immunology, Chelsea and Westminster Hospital, Imperial College London, London, U.K. 3 Imperial College School of Medicine, Chelsea and Westminster Hospital, Imperial College London, London, UK. Abstract Toll-like receptors (TLRs) play a critical role in innate immune responses against invading pathogens. However, the role and regulation of TLRs during KSHV infection remain poorly understood. We demonstrate that TLR4 mediates innate response against KSHV and that KSHV targets TLR4 expression as a mechanism of immune evasion. In vitro, mouse macrophages or human lymphatic endothelial cells lacking TLR4 are more susceptible to KSHV infection, whereas activation of TLR4-mediated signalling with bacterial lipopolysaccharide protects cells from KSHV infection. In vivo, HIV-1-infected individuals who carry a non-functional TLR4 allele appear more likely to have multicentric Castleman’s disease, a lymphoproliferation associated with enhanced KSHV replication. Furthermore, we show that KSHV has evolved mechanisms to evade the TLR4-mediated response. The KSHV-encoded vIRF1 and vGPCR co-operate to suppress TLR4 expression in human lymphatic endothelial cells. Notably, ERK activation by vGPCR or by viral attachment to the cell membrane results in rapid TLR4 down-regulation. Our findings reveal the first example of viral immune evasion through suppression of TLR4 expression and suggest the potential use of TLR4 agonists for treatment of KSHV-related neoplasms. Presenting author Email: d.lagos@ucl.ac.uk 33
Page 1 and 2: The 11 th International Workshop on
Page 3 and 4: Scientific Programme Committee Davi
Page 7 and 8: Travel Directions and Maps The 11 t
Page 9 and 10: By rail The 11 th International Wor
Page 11 and 12: Agenda The 11 th International Work
Page 13 and 14: Wednesday, July 23 rd The 11 th Int
Page 15 and 16: Thursday, July 24 th The 11 th Inte
Page 17 and 18: Friday July 25 th The 11 th Interna
Page 31: The 11 th International Workshop on
Page 83 and 84:
The 11 th International Workshop on
Page 85 and 86:
Page 87 and 88:
Page 89 and 90:
Page 91 and 92:
Page 93 and 94:
Page 95 and 96:
Page 97 and 98:
Page 99 and 100:
Page 101 and 102:
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Adam Grundhhoff Friedensallee 63 Ha
Page 119 and 120:
Dan Frampton Department of Infectio
Page 121 and 122:
Fang Cheng Vuolukiventie 1b g145 He
Page 123 and 124:
Keiji Ueda Dept.of Infectious Disea
Page 125 and 126:
Prof Juergen Haas Max-von-Pettenkof
Page 127 and 128:
Vladimir Majerciak 4817 36th Street
Page 129 and 130:
Page 131 and 132:
Page 133:
show all

Contents - College of Medical and Dental Sciences - University of ...

Create successful ePaper yourself

Delete template?

Save as template?