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

More documents

Recommendations

Info

The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK Virus-Cell Interactions II Abstract 60 KAPOSI’S SARCOMA ASSOCIATED HERPESVIRUS (KSHV/HHV-8) FORMS A MULTI-MOLECULAR COMPLEX OF INTEGRINS (αVβ5, αVβ3 AND α3β1), CD98 AND XCT DURING INFECTION OF HUMAN DERMAL MICROVASCULAR ENDOTHELIAL (HMVEC-D) CELLS Mohanan Valiya Veettil, Fu-Zhang Wang, Sathish Sadagopan, Neelam Sharma-Walia, Hari Raghu, Laszlo Varga and Bala Chandran Presenting author. H.M. Bligh cancer research laboratories, Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA Abstract Baculovirus expressed purified KSHV-gB mediated the adhesion of HMVEC-d, HFF, CV-1 and HT-1080 cells. Anti-αV and β1 integrin antibodies inhibited the cell adhesion. Variable levels of neutralization of HMVEC-d and HFF cell infection was observed with anti- αVβ3 and αVβ5 integrin antibodies, and variable levels of inhibition of virus entry in four adherent cell types was observed with soluble integrins. Virus binding and DNA internalization studies suggest that αVβ3 and αVβ5 integrins play roles in KSHV entry. We observed time dependent temporal KSHV interactions with HMVEC-d cell integrins, CD98 and xCT. Integrin αvβ5 interaction with CD98 predominantly occurred by 1’ postinfection (PI) and dissociated at 10’ PI, whereas α3β1-CD98 interaction was maximum at 10’ PI which dissociated at 30’ PI, and αvβ3 -CD98 interaction was maximum at 10’ PI and retained at the observed 30’ PI. Confocal microscopy studies demonstrated the association of CD98/xCT with α3β1 and KSHV. Pre-incubation of KSHV with soluble heparin and α3β1 significantly inhibited this association. KSHV infection activated FAK and Src co-localized with CD98 at the plasma membranes of infected cells. Anti-CD98 and xCT antibodies did not block virus binding and entry; however, viral gene expression was significantly inhibited suggesting that CD98-xCT play roles in post entry-stage of infection. Together, these studies suggest that KSHV interacts with functionally related integrins (αvβ5, α3β1 and αvβ3) and CD98/xCT molecules to form a multi-molecular complex during the early stages of endothelial cell infection probably mediating multiple roles in entry, signal transduction and viral gene expression. Presenting author Email: bala.chandran@rosalindfranklin.edu 88
The 11 th International Workshop on KSHV & Related Agents, Birmingham, UK Virus-Cell Interactions II Abstract 61 MURINE GAMMAHERPESVIRUS 68 ESTABLISHES A PERSISTENT INFECTION IN ENDOTHELIAL CELLS A.L. Suárez and L.F. van Dyk University of Colorado Denver School of Medicine, Department of Microbiology, 12800 E 19 th Ave, RC1 North Bldg P18-9401A, Aurora, CO 80010, USA Abstract Gammaherpesvirus associated diseases occur predominately in immunocompromised individuals. Gammaherpesvirus infection of cells usually results either in productive lytic infection, characterized by expression of all viral genes and complete cell lysis, or in latent infection, in which few viral genes are expressed and no cell lysis occurs. Herpesvirus infections must traverse endothelial cell (EC) barriers, and infection of ECs is important to the pathogenesis of both human cytomegalovirus and Kaposi’ sarcoma associated virus. The role of ECs in the mouse model system, gammaherpesvirus 68 (gHV68), has not been previously characterized. Recently, we demonstrated that ECs were unique in that a significant proportion of the cells escaped lysis, remained viable and proliferated in culture, but continued to produce infectious virus. Infected ECs were altered in adherence, morphology and surface marker expression. However, infected ECs maintained MHC class I expression, suggesting that EC contribution to pathogenesis is likely limited to immunodeficient states. Primary ECs also supported productive infection with enhanced survival, and we are now investigating ECs as a source of persistent infection in vivo. From a panel of gHV68 mutants, we identified several viral oncogenes which promote survival of infected ECs. Intriguingly, the viral genes which promote EC survival have previously been characterized as important in latency, but dispensable for lytic infection. Our data reveal a cell type specific outcome of gHV68 infection which can provide an ongoing source of virus production. gHV68 infection of ECs provides a facile screen for viral persistence genes and investigation of EC infection in pathogenesis. Presenting author Email: andrea.suarez@uchsc.edu 89
Page 1 and 2:
The 11 th International Workshop on
Page 3 and 4:
Scientific Programme Committee Davi
Page 5 and 6:
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 19 and 20:
Page 21 and 22:
Page 23 and 24:
Page 25 and 26:
Page 27 and 28:
Page 29 and 30:
Page 31 and 32:
Page 33 and 34:
Page 35 and 36:
Page 37 and 38: The 11 th International Workshop on
Page 87: The 11 th International Workshop on
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 133: The 11 th International Workshop on
show all

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

Create successful ePaper yourself

Delete template?

Save as template?