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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
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