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Mechanisms of Oncogenesis by Gammaherpesvirus
Mechanisms Involved in the Maintenance of KSHV Episomes During Host Cell Division
EBNA3C Targeting of the Alpha Integrin Promoter :The Potential Molecular Link Between EBV and Metastisis
EBNA3C's role in deregulation of the cell cycle
Mechanism of Inhibition of Viral Lytic Replication by Kaposi's Sarcoma Associated Herpesvirus Encoded Latency Associated Nuclear Antigen
Inhibiton of the Anti-metastatic Effects of Nm23: A Potential Molecular Link Between EBV and Metastisis
Construction of a KSHV-GFP Recombinant Virus and the Development of a System to Assess Gene functions of KSHV
Modulation of Cox-2 expression (an indicator of metastasis) by Nm23H1(a known suppressor of Metastasis)
Kaposi Sarcoma Associated Herpesvirus:- Elucidation of the Mechanism of the Latent DNA Replication
Development of an in vivo animal model for evaluation of the role of Nm23H1 and EBNA proteins on the ability of cell lines to metastasize in mice. Link Between EBV and Metastasis
| Construction of a KSHV-GFP Recombinant Virus and the Development of a System to Assess Gene functions of KSHV |
| Ke Lan, MD, PhD |
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Kaposi's sarcoma associated herpesvirus(KSHV), also designated HHV8 was
discovered in 1994. Epidemiological studies have demonstrated that KSHV
is the causative agent for KS. For instance, DNA sequences of this virus
were consistently found in KS lesions of all epidemiological forms.
Furthermore, serological assays suggest that KSHV is not ubiquitous but
is closely associated with those people at risk for developing KS. In
addition to KS tumors, KSHV is also found in B-cell primary effusion
lymphomas or body cavity based lymphomas and in some forms of
Multicentric Castleman Disease, a B-cell lymphoproliferative disorder.
The discovery of the genome of KSHV was a major breakthrough in our
understanding of the pathogenesis of these diseases. Unique among human
herpesvirus, KSHV encodes a number of cytokines, cyclin homologues,
G proteins, moreover, unlike Epstein-Barr virus encoded EBNA2, EBNA3 and
LMPs, which are latent genes, the KSHV cytokine signaling genes are
expressed in lytic stage, so lytic replication of the virus appears to
be important not only for viral propagation but also for viral
pathogenicity, however, the proteins and genomic elements that control
activation and completion of the viral lytic cycle are only partly
understood. In addition, most data regarding the transforming potential
of this virus have been derived from experiments with single viral gene
products, nothing is known about the function of these gene products in
the context of the whole virus. In particular, it remain unclear whether
all or only certain viral transforming proteins are required for
cellular transformation. The major goal of this project is to construct
a KSHV-GFP recombinant virus by homologous recombination strategy.
This KSHV-GFP recombinant virus will facilitate tracking the infected
cells during the process of lytic primary infection and further to
elucidate the mechanism of interaction between virus and host cells.
Moreover, based on this recombinant virus, a series KSHV mutants can be
made for analysis of the functions of specific genes. |
