Staff by Division
Staff Biography
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Lindsey Hutt-Fletcher, Ph.DProfessor
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ContactPhone:
(318) 675-4948 Team Membership |
Education / Research / Publications
Education / Professional Experience
Postdoctoral Study, University of North Carolina at Chapel Hill
Ph.D., Virus Immunology, 1973, University of London
B.Sc., Bacteriology, 1968, University of Liverpool
Research Interest
Virus cell interactions, pathogenesis of oncogenic EBV
Long standing research interests are in virus cell interactions and virus pathogenesis, particularly in the biology of Epstein-Barr virus (EBV). EBV is an oncogenic human herpesvirus that establishes persistent infections in almost 100% of the world's population. Most people are infected subclinically in childhood. However, the virus also causes infectious mononucleosis, oral hairy leukoplakia and immunoblastic lymphoma and is strongly implicated in the development of Burkitt's lymphoma, nasopharyngeal carcinoma, gastric carcinoma and Hodgkin's Disease. EBV has two major cellular targets, B lymphocytes and epithelial cells. Our long term goal is to understand how the virus enters and exits these target cells and how it spreads within and between its human hosts. Studies focus on the functions of the envelope glycoproteins critical to these processes and on the cellular proteins with which they interact.
Major Research Interests
Pathogenesis of tumor viruses
Virus spread
Virus entry
Virus assembly
Virus cell interactions
Cellular receptors for virus glycoproteins
Project 1, B cell lymphomas and EBV-associated epithelial cancers: This project examines issues important to the basic virology of EBV. Specifically, the roles that EBV glycoproteins gB and gNgM play in assembly of virus are being studied. The roles of gB in capsid maturation and fusion with the outer nuclear membrane and the role of gNgM in secondary envelopment are the major focus.
Project 2, oral malignancies associated with EBV: This project continues work on the role that the gHgLgp42 glycoprotein complex of Epstein-Barr virus plays in entry of virus into B cells and epithelial cells, explores the role that CR2 may play in infection of oral malignant and premalignant lesions and examines the importance of integrin binding proteins in the EBV envelope to epithelial cell entry and signaling.
Project 3, EBV-associated oral malignancies in AIDS patients: This project follows up on our observation that antibodies to the major EBV glycoprotein gp350/220 which block attachment to B cells can enhance infection of epithelial cells. The contribution made by such antibodies, found at high levels in saliva of HIV positive individuals, to spread of virus in the oropharynx is being evaluated and the mechanism by which they act is being explored. One hypothesis being tested is that gp350/220, which is dispensable for epithelial cell infection, impedes access of other more relevant glycoproteins to the cell surface. We have evidence to suggest that antibodies capable of cross-linking gp350/220 may cluster the protein in the virus membrane and thereby enhance such access.
Selected Publications
Molesworth S.J., Lake, C.M., Borza, C.M., Turk, S.M., Hutt-Fletcher, L.M. 2000. Epstein-Barr virus gH is essential for penetration of B cells but also plays a role in attachment of virus to epithelial cells. J. Virol. 74:6324-6332.
Lake, C.M., Hutt-Fletcher, L.M. 2000. Epstein-Barr virus that lacks glycoprotein gN is impaired in assembly and infection. J. Virol. 74:11162-11172.
Borza, C.M., and Hutt-Fletcher, L.M. 2002. Alternate replication in B cells and epithelial cells switches Epstein-Barr virus tropism. Nature Medicine, 8:594-599.
Lake, C.M. and Hutt-Fletcher, L.M. 2004. The Epstein-Barr virus BFRF1 and BFLF2 proteins interact and coexpression alters their cellular localization, Virology, 320:99-106.
Borza, C.M., Morgan A.J., Turk, S.M. and Hutt-Fletcher L.M. 2004. Use of gHgL for attachment of Epstein-Barr virus to epithelial cells compromises infection, J. Virol. 78:5007-5014.
Hutt-Fletcher, L.M. 2005. EBV entry and epithelial infection. In “Infection, Pathogenesis, Molecular Biology and Control of Epstein-Barr Virus”, Ed. Robertson, E. S., Caister Academic Press, Norfolk, England, p359-378.
Wu, L., Borza, C.M., and Hutt-Fletcher. 2005. Mutations of Epstein-Barr virus gH that are differentially able to support fusion with B cells or epithelial cells. J. Virol. 79:10923-10930.
Jiang, R., Scott, R.S. and Hutt-Fletcher, L.M. 2006. Epstein-Barr virus shed in saliva is high in the B cell tropic glycoprotein gp42. J. Virol. 80:7281-7283.
Turk, S.M., Jiang, R., Chesnokova, L.S., and Hutt-Fletcher, L.M. 2006 Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells. J. Virol. 80:9628-9633.
Wu, L., and Hutt-Fletcher, L.M. 2007. Compatibility of the gH homologs of Epstein-Barr virus and related lymphocryptoviruses. J. Gen Virol., 88:2129-2136.
Hutt-Fletcher, L.M. 2007. Epstein-Barr virus entry. J. Virol., 81:7825-7832.