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Research Themes |
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 Molecular
biology and pathogenesis of Human Herpes virus
8
Molecular
biology and pathogenesis of Human Herpes virus
6
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Research Projects |
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>>
MOLECULAR BIOLOGY
AND PATHOGENESIS OF HUMAN HERPES VIRUS 8
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Kaposi's sarcoma (KS) is an angioproliferative
disease observed in elderly men of Mediterranean
origin (classical KS), in Africa (endemic KS)
and in individuals infected with the human immunodeficiency
virus (HIV) (AIDS-KS). The risk factor for developing
KS is several times greater if seropositive for
HIV-1, suggesting that HIV-1 infection, directly
or indirectly, contributes to KS development.
In addition, classical and endemic KS are rather
mild compared to the AIDS-KS, which is very aggressive.
Recent epidemiological data have linked the human
herpes virus 8 (HHV-8) to all forms of KS with
more than 95% of all KS lesions examined were
positive for HHV-8 DNA sequences. Moreover, the
detection of HHV-8 DNA in the peripheral blood
mononuclear cells (PBMC) of AIDS patients appears
predictive of KS development. These data strongly
support a role for HHV-8 in the development of
KS. My laboratory is currently studying the biology
of v-Flip, v-Cyclin and LANA-1, three latency-associated
proteins of HHV-8 in order to understand how these
can contribute to pathogenesis. Furthermore, with
the use of specific mutants, our goal is to identify
HHV-8 genes that are essential for viral transformation/immortalization
of primary endothelial cells. Lastly, the role
of HIV-1 and HIV-1 associated proteins in HHV-8
infection and immortalization process is investigated.
These
projects are supported by grants from the
Canadian Institutes of Health Research (CIHR)
and the
National Cancer Institute of Canada.
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>> MOLECULAR
BIOLOGY AND PATHOGENESIS OF HUMAN HERPES VIRUS 6 |
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Herpes viruses are
complex pathogens and like all viruses, they strictly
depend on host cells to propagate themselves. As
with most DNA viruses, many events of the Herpes
virus life cycle take place in the nucleus of the
infected cell. The Immediate-Early (IE) proteins,
translated into the cytoplasm, must travel back
to the nucleus, interact with the nuclear pore complex
and reach the nucleoplasm to continue the infectious
process. Considering that the IE proteins are the
first to be synthesized within the infected cells
and that they play a crucial role in the success
of the infectious process, the Herpes virus IE proteins
are actively studied. For the past several years
our laboratory has focused on the use of human Herpes
virus 6 (HHV-6) as a model for -Herpes virus infection.
Lately, our research efforts were devoted to an
understanding of the functions of IE proteins and
we recently reported on the cloning and the initial
characterization of HHV-6 two major IE proteins,
IE1 and IE2. Over the next few years we propose
to extend our knowledge of the IE proteins and dissect
their close association with the nuclear import
and the transcriptional machineries.
This
project is supported by
the Canadian Institutes of Health Research (CIHR).
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Selected references |
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Gravel, A., Gosselin,
J., and Flamand
L. 2002. Human Herpesvirus 6 immediate-early
1 protein is a sumoylated nuclear phophoprotein
co-localizing with promyelocytic leukemia protein-associated
nuclear bodies. J.
Biol.Chemistry. 277: 19679-19687. PubMed
Link
Cloutier, N., Grandvaux, N., and Flamand, L. 2007. Synergistic activation of interferon-beta gene transcription by the viral FLICE inhibitory protein of Kaposi's sarcoma-associated herpesvirus and type I IFN activators. Eur. J. Immunol. 37:2772-2778. PubMed
Link
Flamand, L., Tremblay, M.J., and Borgeat, P. 2007. Leukotriene B4 triggers the in vitro and in vivo release of potent antimicrobial agents. J. Immunol. 178:8036-8045. PubMed
Link
Jaworska, J., Gravel, A., Fink, K., Grandvaux, N., and Flamand, L. 2007. Inhibition of transcription of the beta interferon gene by the human herpesvirus 6 immediate-early 1 protein. J. Virol. 81:5737-5748. PubMed
Link
Lefort, S., Soucy-Faulkner, A., Grandvaux, N., and Flamand, L. 2007. Binding of Kaposi's sarcoma-associated herpesvirus K-bZIP to interferon-responsive factor 3 elements modulates antiviral gene expression. J. Virol. 81:10950-10960. PubMed
Link
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List of Publications - PubMed
Link
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Additional Information Details |
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