Edward A. Berger, Ph.D.Building 33, Room 1E19A.233 North DriveBethesda, MD 20892-3210Phone: 301-402-2481Fax: email@example.com
Chief, Molecular Structure Section, LVD
My laboratory has had a long-standing interest in how enveloped viruses enter target cells. We seek to unravel the basic mechanisms of membrane fusion mediated by the interactions of viral envelope glycoproteins with their target cell receptors and to apply our knowledge to the development of novel strategies to treat and prevent virus infection. We have had a major focus on HIV but have expanded our studies to diverse enveloped viruses of significance to human health, including other viruses with enhanced pathogenesis in the context of HIV infection, e.g., Kaposi’s sarcoma-associated herpesvirus (KSHV) and hepatitis C virus (HCV), as well as viruses of importance for biodefense.
We developed specialized expression and reporter gene technologies to study membrane fusion mediated by viral glycoproteins and to screen cDNA libraries for essential cellular receptors. These approaches enabled us to discover the first HIV coreceptor, fusin (subsequently renamed CXCR4), followed by the second major coreceptor, CCR5. With this information, we have probed the sequential steps by which HIV Env interaction with CD4 and coreceptor triggers membrane fusion and virus entry and the implications for vaccines based on neutralizing antibodies. Our findings led us to devise a novel genetically engineered protein called sCD4-17b that potently neutralizes HIV; this protein has potential applications in the prevention of HIV infection in the context of topical microbicides and vector-mediated immunoprophylaxis. We are also developing approaches to eradicate, or at least control, the HIV-infected cell reservoirs that persist despite potent antiretroviral therapy; our approaches include the development of immunotoxins and adoptive transfer of engineered CD8 T cells to selectively kill HIV-infected cells.
A major current focus involves mechanistic structure/function analyses of the HIV Env glycoprotein in its native trimeric state. For example, in collaborative study we probed a question related to antibody epitopes that are exposed on monomeric gp120 but masked in the native trimer. By combining a novel functional complementation assay with co-expression of Env constructs harboring specific mutations, we demonstrated that masking of epitopes on the third variable loop (V3) by the first and second variable loops (V1V2) occurs within the same subunit (i.e., intraprotomer, or "cis" masking) rather than between neighboring subunits (interprotomer, or "trans" masking). In a related collaborative project, we have uncovered new interactions within gp120 that we believe reflect its conformation in the functional Env trimer prior to CD4 binding.
A recent new focus in KSHV biology is aimed at understanding the mechanism(s) involved in B-cell infection. Though B cells are major KSHV reservoirs in infected people, and the virus is etiologically linked to two B cell lymphoproliferative disorders (primary effusion lymphoma and mullticentric Castleman's disease), transformed B-cell lines are notoriously refractory to KSHV infection. We have identified a human B-cell line that displays unusually high permissiveness for KSHV infection; we anticipate this will provide an insightful model for the study of infection of this most highly relevant KSHV target cell type.
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Dr. Berger earned his B.S. in chemistry from City College of the City University of New York in 1968. He received his Ph.D. in biochemistry and molecular biology in 1973 from Cornell University. He went on to do a postdoctoral fellowship in the department of genetics, biochemistry, and neurobiology at Stanford University School of Medicine from 1973 to 1976 and another fellowship in the department of cellular and developmental immunology at Scripps Clinical and Research Foundation from 1976 to 1977. He was a staff scientist with the Cell Biology Group at the Worcester Foundation for Experimental Biology, Shrewsbury, Massachusetts, from 1977 to 1987. He joined the Laboratory of Viral Diseases in 1987 and became chief of the Molecular Structure Section in 1995.
American Academy of Microbiology Fellow; Bernard Fields Memorial Lectureship, CROI 2007;1st NIH World AIDS Day Award 2006; ISI Highly Cited Researcher, Breakthrough of the Year, Science 1996; AAAS-Newcomb Cleveland Prize 1997; Great Experiments; Kenneth Fong/Clontech Award; Novartis-Drew Award for Biomedical Science; Damon Runyon-Walter Winchell Foundation Most Prominent Alumni; AMA/NIAID Nathan Davis Award; NIH Outstanding Contributions to Education of Postbaccalaureate Trainees; Norman P Salzman Memorial Mentor Award in Virology, Honorable Mention
Virology Interest Group, Immunology Interest Group, Antibody Interest Group, Viral Hepatitis Interest Group
Liu L, Cimbro R, Lusso P, Berger EA. Intraprotomer masking of third variable loop (V3) epitopes by the first and second variable loops (V1V2) within the native HIV-1 envelope glycoprotein trimer. Proc Natl Acad Sci U S A. 2011 Dec 13;108(50):20148-53.
Cai Y, Berger EA. An immunotoxin targeting the gH glycoprotein of KSHV for selective killing of cells in the lytic phase of infection. Antiviral Res. 2011 Jun;90(3):143-50.
Triyatni M, Berger EA, Saunier B. A new model to produce infectious hepatitis C virus without the replication requirement. PLoS Pathog. 2011 Apr;7(4):e1001333.
Lagenaur LA, Villarroel VA, Bundoc V, Dey B, Berger EA. sCD4-17b bifunctional protein: extremely broad and potent neutralization of HIV-1 Env pseudotyped viruses from genetically diverse primary isolates. Retrovirology. 2010 Feb 16;7:11.
Alkhatib G, Combadiere C, Broder CC, Feng Y, Kennedy PE, Murphy PM, Berger EA. CC CKR5: a RANTES, MIP-1α, MIP-1ß receptor as a fusion cofactor for macrophage-tropic HIV-1. Science. 1996 Jun 28;272(5270):1955-8.
Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996 May 10;272(5263):872-7.
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Last Updated November 01, 2012