Dean H. Kedes
- PhD, Yale University
- MD, Yale School of Medicine
- BS, Stanford University
- Professor, Microbiology, Immunology, and Cancer Biology
- Phone: 434-243-2758
- Email: firstname.lastname@example.org
- Website: http://bims.virginia.edu/faculty/dean-h-kedes/
Human Herpes virus associated with malignancy, including Kaposi's Sarcoma
Pathogenesis of Kaposi's Sarcoma-Associated Herpesvirus
Kaposi's sarcoma (KS) remains one of the two most common AIDS-associated malignancies and is caused by the human herpesvirus, KSHV, first discovered in 1994. Nevertheless, many details of KSHV infection and pathogenesis remain unclear. A rare type of B cell lymphoma (PEL) also arising from KSHV infection, has allowed the development of cell lines that produce KSHV in culture. These lines, along with a manipulable bacterial artificial chromosome of the approximately 165kbp viral genome, have allowed the study of viral structure, assembly, gene expression and pathogenesis. Examining both KSHV and its close non-human primate pathogen, rhesus monkey rhadinovirus (RRV), we have focused on the following four major areas:
1. Viral gene culprits: Isolation and characterization of viral genes and their protein products involved in KSHV pathogenesis. In particular we are interested in the mechanisms underlying a) the activation of cellular signaling during viral entry and b) the pathway of viral egress, including the affects of viral gene products on the cytoskeleton.
2. Viral structure and proteomics: Determination of the protein composition, spatial arrangement and assembly of viral and subviral particles. Our approaches include the coupling of classical molecular biology and virology with biochemistry, electron microscopy (EM), and, through collaborations with colleagues that include Pew Scholar, Z. Hong Zhu (UCLA), immuno-EM and cryo-EM.
3. Viral tropism in patients: Identification of the cell types initially infected during primary transmission of KSHV in humans.
4. Investigations into the structural connection between viral and human genomes during latent (chronic) infection, in a collaborative effort with the laboratory of Mitchell Smith and using sub-nanometer microscopy.
- Grant M, Loftus M, Stoja A, Kedes D, Smith M. Superresolution microscopy reveals structural mechanisms driving the nanoarchitecture of a viral chromatin tether. Proceedings of the National Academy of Sciences of the United States of America. 2018;115(19): 4992-4997. PMID: 29610353 | PMCID: PMC5948984
- Loftus M, Verville N, Kedes D. A Conserved Leucine Zipper Motif in Gammaherpesvirus ORF52 Is Critical for Distinct Microtubule Rearrangements. Journal of virology. 2017;91(17). PMID: 28615210 | PMCID: PMC5553167
- Anderson M, Loftus M, Kedes D. Maturation and vesicle-mediated egress of primate gammaherpesvirus rhesus monkey rhadinovirus require inner tegument protein ORF52. Journal of virology. 2014;88(16): 9111-28. PMID: 24899183 | PMCID: PMC4136283
- Ellison T, Kedes D. Variable episomal silencing of a recombinant herpesvirus renders its encoded GFP an unreliable marker of infection in primary cells. PloS one. 2014;9(11): e111502. PMID: 25402328 | PMCID: PMC4234296
- Woodson E, Anderson M, Loftus M, Kedes D. Progressive Accumulation of Activated ERK2 within Highly Stable ORF45-Containing Nuclear Complexes Promotes Lytic Gammaherpesvirus Infection. PLoS pathogens. 2014;10(4): e1004066. PMID: 24722398 | PMCID: PMC3983062
- Zhou Z, Hui W, Shah S, Jih J, O'Connor C, Sherman M, Kedes D, Schein S. Four levels of hierarchical organization, including noncovalent chainmail, brace the mature tumor herpesvirus capsid against pressurization. Structure (London, England : 1993). 2014;22(10): 1385-98. PMID: 25220471
- Borah S, Nichols L, Hassman L, Kedes D, Steitz J. Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry. RNA (New York, N.Y.). 2012;18(8): 1573-9. PMID: 22745225 | PMCID: PMC3404377
- Woodson E, Kedes D. Distinct roles for extracellular signal-regulated kinase 1 (ERK1) and ERK2 in the structure and production of a primate gammaherpesvirus. Journal of virology. 2012;86(18): 9721-36. PMID: 22740395 | PMCID: PMC3446570
- Hassman L, Ellison T, Kedes D. KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation. The Journal of clinical investigation. 2011;121(2): 752-68. PMID: 21245574 | PMCID: PMC3026728
- Nichols L, Adang L, Kedes D. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumor activity of an immunosuppressant drug. PloS one. 2011;6(1): e14535. PMID: 21264294 | PMCID: PMC3021514
- Deng B, O'Connor C, Kedes D, Zhou Z. Cryo-electron tomography of Kaposi's sarcoma-associated herpesvirus capsids reveals dynamic scaffolding structures essential to capsid assembly and maturation. Journal of structural biology. 2008;161(3): 419-27. PMID: 18164626 | PMCID: PMC2692512
- Adang L, Tomescu C, Law W, Kedes D. Intracellular Kaposi's sarcoma-associated herpesvirus load determines early loss of immune synapse components. Journal of virology. 2007;81(10): 5079-90. PMID: 17329329 | PMCID: PMC1900224
- Adang L, Parsons C, Kedes D. Asynchronous progression through the lytic cascade and variations in intracellular viral loads revealed by high-throughput single-cell analysis of Kaposi's sarcoma-associated herpesvirus infection. Journal of virology. 2006;80(20): 10073-82. PMID: 17005685 | PMCID: PMC1617294
- O'Connor C, Kedes D. Mass spectrometric analyses of purified rhesus monkey rhadinovirus reveal 33 virion-associated proteins. Journal of virology. 2006;80(3): 1574-83. PMID: 16415032 | PMCID: PMC1346966
- O'Connor C, Kedes D. Rhesus monkey rhadinovirus: a model for the study of KSHV. Current topics in microbiology and immunology. 2006;312 43-69. PMID: 17089793
- Parsons C, Adang L, Overdevest J, O'Connor C, Taylor J, Camerini D, Kedes D. KSHV targets multiple leukocyte lineages during long-term productive infection in NOD/SCID mice. The Journal of clinical investigation. 2006;116(7): 1963-73. PMID: 16794734 | PMCID: PMC1481659