Research Topics
Genomes and GenesSpecies | Samuel H SpeckSummaryAffiliation: Emory University Country: USA Publications
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Publications
Maintenance of gammaherpesvirus latency requires viral cyclin in the absence of B lymphocytesLinda F van Dyk
Department of Microbiology and Immunology, University of Colorado Health Science Center, Denver 80262, USA
J Virol 77:5118-26. 2003....- NF-kappaB p50 plays distinct roles in the establishment and control of murine gammaherpesvirus 68 latencyLaurie T Krug
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, 1462 Clifton Road, Suite 429, Atlanta, GA 30322, USA
J Virol 83:4732-48. 2009..Taken together, these data demonstrate that p50 is required for immune control by the host and has distinct tissue-dependent roles in the regulation of murine gammaherpesvirus latency during chronic infection... - Murine gamma-herpesvirus immortalization of fetal liver-derived B cells requires both the viral cyclin D homolog and latency-associated nuclear antigenXiaozhen Liang
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA
PLoS Pathog 7:e1002220. 2011.... - Identification of spliced gammaherpesvirus 68 LANA and v-cyclin transcripts and analysis of their expression in vivo during latent infectionRobert D Allen
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, 954 Gatewood Rd, NE, Atlanta, GA 30329, USA
J Virol 80:2055-62. 2006.... - A gammaherpesvirus-secreted activator of Vbeta4+ CD8+ T cells regulates chronic infection and immunopathologyAndrew G Evans
Emory Vaccine Center, Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Exp Med 205:669-84. 2008.... - Murine gammaherpesvirus 68 LANA is essential for virus reactivation from splenocytes but not long-term carriage of viral genomeClinton R Paden
Emory Vaccine Center, Emory University School of Medicine, 1452 Clifton Road, Suite 429, Atlanta, GA 30322, USA
J Virol 84:7214-24. 2010..Thus, these data provide the first evidence that a LANA homolog is directly involved in the formation and/or maintenance of an extrachromosomal viral episome in vivo, which is likely required for the reactivation of MHV68... - Control of virus reactivation arrests pulmonary herpesvirus-induced fibrosis in IFN-gamma receptor-deficient miceAna L Mora
Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Emory University, 615 Michael Street, Suite 205K, Atlanta, GA 30322, USA
Am J Respir Crit Care Med 175:1139-50. 2007..Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic lung disorder of unknown cause. Several studies suggest an association between Epstein-Barr virus pulmonary infection and the development of IPF... - Systematic mutagenesis of the murine gammaherpesvirus 68 M2 protein identifies domains important for chronic infectionJeremy H Herskowitz
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30329, USA
J Virol 82:3295-310. 2008..Taken together, these analyses will aide future studies for identifying M2 interacting partners and B-cell signaling pathways that are manipulated by the M2 protein... - Role for MyD88 signaling in murine gammaherpesvirus 68 latencyLisa M Gargano
Department of Microbiology and Immunology, Emory University School of Medicine, 1462 Clifton Road, Suite 429, Atlanta, GA 30329, USA
J Virol 82:3853-63. 2008..These data provide evidence for a unique role for MyD88 in the establishment of MHV68 latency... - Alternatively initiated gene 50/RTA transcripts expressed during murine and human gammaherpesvirus reactivation from latencyKathleen S Gray
Emory Vaccine Center, 1462 Clifton Road, Suite 429, Atlanta, GA 30322, USA
J Virol 83:314-28. 2009.... 
The M4 gene of gammaHV68 encodes a secreted glycoprotein and is required for the efficient establishment of splenic latencyAndrew G Evans
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University, 954 Gatewood Rd. NE, Atlanta, GA 30329, USA
Virology 344:520-31. 2006..These results suggest that M4 mediates an extracellular host-pathogen interaction that impacts the establishment of latent infection in the spleen, but not the peritoneum...- Inhibition of NF-kappaB signaling reduces virus load and gammaherpesvirus-induced pulmonary fibrosisLaurie T Krug
Department of Microbiology and Immunology, Emory University, Atlanta, Georgia, USA
Am J Pathol 177:608-21. 2010..Host determinants of latency might therefore represent new therapeutic targets for gammaherpesvirus-associated pulmonary fibrosis... - The murine gammaherpesvirus 68 M2 gene is required for efficient reactivation from latently infected B cellsJeremy Herskowitz
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, School of Medicine, Emory University, Atlanta, GA 30329, USA
J Virol 79:2261-73. 2005.... - Inhibition of NF-kappaB activation in vivo impairs establishment of gammaherpesvirus latencyLaurie T Krug
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Pathog 3:e11. 2007.... - Identification of an Rta responsive promoter involved in driving gammaHV68 v-cyclin expression during virus replicationRobert D Allen
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
Virology 365:250-9. 2007.... - Role of B-cell proliferation in the establishment of gammaherpesvirus latencyJanice M Moser
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, GA 30329, USA
J Virol 79:9480-91. 2005..Thus, the studies provide direct evidence that the proliferation of latently infected B cells is critical for the establishment of chronic gammaHV68 infection... - ORF73-null murine gammaherpesvirus 68 reveals roles for mLANA and p53 in virus replicationJ Craig Forrest
Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, 1462 Clifton Rd, Atlanta, GA 30322, USA
J Virol 81:11957-71. 2007..Overall, these data demonstrate the importance of mLANA in MHV68 replication and suggest that LANA proteins limit the induction of cellular stress responses to regulate the viral gene expression cascade and limit host cell injury... - Gammaherpesvirus-driven plasma cell differentiation regulates virus reactivation from latently infected B lymphocytesXiaozhen Liang
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Pathog 5:e1000677. 2009.... - The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiationAndrea M Siegel
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Pathog 4:e1000039. 2008..Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a strategy that appears to be conserved between at least EBV and MHV68... - Identification of closely spaced but distinct transcription initiation sites for the murine gammaherpesvirus 68 latency-associated M2 geneMark DeZalia
Emory Vaccine Center, Emory University School of Medicine, 1462 Clifton Road, Atlanta, GA 30322, USA
J Virol 82:7411-21. 2008..This initial detailed analysis of M2 gene transcription in vivo will aid future studies on regulation of M2 gene expression... - The de novo methyltransferases DNMT3a and DNMT3b target the murine gammaherpesvirus immediate-early gene 50 promoter during establishment of latencyKathleen S Gray
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Virol 84:4946-59. 2010.... - A gammaherpesvirus 68 gene 50 null mutant establishes long-term latency in the lung but fails to vaccinate against a wild-type virus challengeJanice M Moser
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, 954 Gatewood Road NE, Atlanta, GA 30329, USA
J Virol 80:1592-8. 2006..These data indicate gammaherpesviruses that are unable to undergo lytic replication in vivo may not be viable vaccine candidates despite the detection of cells harboring viral genome at late times postinfection... - Signaling through Toll-like receptors induces murine gammaherpesvirus 68 reactivation in vivoLisa M Gargano
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Virol 83:1474-82. 2009.... - Blimp-1-dependent plasma cell differentiation is required for efficient maintenance of murine gammaherpesvirus latency and antiviral antibody responsesAndrea M Siegel
Emory Vaccine Center and Department of Microbiology, 1462 Clifton Road, Suite 429, Atlanta, GA 30329, USA
J Virol 84:674-85. 2010.... - The gammaherpesvirus 68 latency-associated nuclear antigen homolog is critical for the establishment of splenic latencyNathaniel J Moorman
Division of Microbiology and Immunology and The Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, Atlanta, Georgia 30329, USA
J Virol 77:10295-303. 2003..Thus, consistent with its proposed role in replication of the latent viral episome, LANA appears to be a critical determinant in the establishment of gammaHV68 latency in the spleen post-intranasal infection... - Disruption of gammaherpesvirus 68 gene 50 demonstrates that Rta is essential for virus replicationIglika V Pavlova
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
J Virol 77:5731-9. 2003..This work lays the foundation for characterizing the role of Rta in gamma HV68 chronic infection of mice... - Identification of infected B-cell populations by using a recombinant murine gammaherpesvirus 68 expressing a fluorescent proteinChristopher M Collins
Emory Vaccine Center, Atlanta, Georgia 30322, USA
J Virol 83:6484-93. 2009.... - Characterization of a spontaneous 9.5-kilobase-deletion mutant of murine gammaherpesvirus 68 reveals tissue-specific genetic requirements for latencyEric T Clambey
Division of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, 954 Gatewood Road NE, Atlanta, GA 30329, USA
J Virol 76:6532-44. 2002..These studies highlight the importance of loss-of-function mutations in defining the genetic requirements for the establishment and maintenance of herpesvirus latency... - Unbiased mutagenesis of MHV68 LANA reveals a DNA-binding domain required for LANA function in vitro and in vivoClinton R Paden
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS Pathog 8:e1002906. 2012..Interestingly, each of these mLANA-mutant viruses exhibited phenotypes similar to the mLANA-null mutant virus, indicating that DNA-binding is critical for mLANA function... - Establishment and maintenance of long-term murine gammaherpesvirus 68 latency in B cells in the absence of CD40David O Willer
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, 954 Gatewood Rd N E, Atlanta, GA 30329, USA
J Virol 79:2891-9. 2005..Taken together, these findings are consistent with a model in which chronic virus infection of CD40(-/-) mice is maintained through virus reactivation in the lungs and reseeding of latency reservoirs... - Evidence for CDK-dependent and CDK-independent functions of the murine gammaherpesvirus 68 v-cyclinJason W Upton
Department of Microbiology and Immunology, Emory University School of Medicine, 1462 Clifton Road, Suite 429, Atlanta, GA 30322, USA
J Virol 80:11946-59. 2006..Taken together, these data suggest that lytic replication and reactivation in vivo are differentially regulated by CDK-dependent and CDK-independent functions of v-cyclin, respectively... - Identification of candidate gammaherpesvirus 68 genes required for virus replication by signature-tagged transposon mutagenesisNathaniel J Moorman
Center for Emerging Infectious Diseases, Division of Microbiology and Immunology, Yerkes National Primate Center, Emory University, Atlanta, GA, USA
J Virol 78:10282-90. 2004..Notably, all but one of the candidate essential replication genes identified in this screen have been shown to be essential for the replication of at least one other herpesvirus... - Characterization of omental immune aggregates during establishment of a latent gammaherpesvirus infectionKathleen S Gray
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS ONE 7:e43196. 2012..These data provide the first evidence that the omentum is a site of chronic MHV68 infection that may contribute to the maintenance of chronic infection... - Tracking murine gammaherpesvirus 68 infection of germinal center B cells in vivoChristopher M Collins
Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, United States of America
PLoS ONE 7:e33230. 2012..Finally, we have shown that marking of infected cells with MHV68-H2bYFP is extended long after the onset of latency - which should facilitate studies to track MHV68 latently infected cells at late times post-infection... - Expansion of effector memory TCR Vbeta4+ CD8+ T cells is associated with latent infection-mediated resistance to transplantation toleranceDale Stapler
Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA
J Immunol 180:3190-200. 2008..These results define the viral gene and immune cell types involved in latent infection-mediated resistance to allograft tolerance and underscore the influence of latent herpesviruses on allograft survival... - Murine gammaherpesvirus 68 Rta-dependent activation of the gene 57 promoterIglika Pavlova
Division for Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE, Atlanta, GA 30329, USA
Virology 333:169-79. 2005..Overall, analysis of the gammaHV68 gene 57 promoter suggests that mechanisms of Rta activation are conserved among gamma2-herpesviruses... - Disruption of the gene encoding the gammaHV68 v-GPCR leads to decreased efficiency of reactivation from latencyNathaniel J Moorman
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
Virology 307:179-90. 2003..From these experiments we conclude that the gammaHV68 v-GPCR is dispensable for acute virus replication in vivo, but does play a role in reactivation from latency... - Variable methylation of the Epstein-Barr virus Wp EBNA gene promoter in B-lymphoblastoid cell linesJennifer Elliott
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA
J Virol 78:14062-5. 2004..Taken together, these data argue that other factors, perhaps in conjunction with Wp methylation, play a role in suppressing Wp activity in LCLs... - Viral latency and its regulation: lessons from the gamma-herpesvirusesSamuel H Speck
Emory Vaccine Center, Emory University, Atlanta, GA 30322, USA
Cell Host Microbe 8:100-15. 2010..Here, we review the molecular basis of latency, with special attention to the gamma-herpesviruses, in which the understanding of this process is most advanced... - Long-term latent murine Gammaherpesvirus 68 infection is preferentially found within the surface immunoglobulin D-negative subset of splenic B cells in vivoDavid O Willer
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
J Virol 77:8310-21. 2003..Furthermore, at late times postinfection latent gammaHV68 is largely confined to the surface immunoglobulin D-negative subset of B cells... - Ex vivo stimulation of B cells latently infected with gammaherpesvirus 68 triggers reactivation from latencyJanice M Moser
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, 954 Gatewood Rd, NE, Atlanta, GA 30329, USA
J Virol 79:5227-31. 2005.... - Establishment of B-cell lines latently infected with reactivation-competent murine gammaherpesvirus 68 provides evidence for viral alteration of a DNA damage-signaling cascadeJ Craig Forrest
The Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322, USA
J Virol 82:7688-99. 2008..In addition, such cell lines may be of value in evaluating targeted therapies to gammaherpesvirus-related tumors... - Lung infection with gamma-herpesvirus induces progressive pulmonary fibrosis in Th2-biased miceAna L Mora
Center for Translational Research of the Lung, Division of Pulmonary, Allergy, and Critical Care, Dept of Medicine, Emory Univ, Atlanta, GA 30322, USA
Am J Physiol Lung Cell Mol Physiol 289:L711-21. 2005..In summary, chronic herpesvirus pulmonary infection in IFN-gammaR-/- mice causes progressive pulmonary fibrosis and many of the pathological features seen in IPF... - Characterization of murine gammaherpesvirus 68 v-cyclin interactions with cellular cdksJason W Upton
Center for Emerging Infectious Diseases, Yerkes National Primate Research Center, Emory University School of Medicine, NE Atlanta, GA 30329, USA
Virology 341:271-83. 2005..The latter suggests that, at least in vitro, the gammaHV68 v-cyclin exhibits functional characteristics of both cyclin E and cyclin A... - Synergistic autoactivation of the Epstein-Barr virus immediate-early BRLF1 promoter by Rta and ZtaPingfan Liu
Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, NE, Atlanta, GA 30329, USA
Virology 310:199-206. 2003..Decreasing the amount of transfected Rta expression vector reduced background Rta activation, while retaining specific activation of Rp... - Deletion of Epstein-Barr virus regulatory sequences upstream of the EBNA gene promoter Wp1 is unfavorable for B-Cell immortalizationLina I Yoo
Division of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
J Virol 76:11763-9. 2002..This is the first report of an LCL in which transcription initiation from a Wp downstream of Wp1 has been documented... - Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculationMeagan A Jacoby
Division of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30329, USA
J Virol 76:1790-801. 2002..These results indicate that the requirements for the establishment of latency are affected by the route of infection... - Rapid demethylation of the IFN-gamma gene occurs in memory but not naive CD8 T cellsEllen N Kersh
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA
J Immunol 176:4083-93. 2006.... - Critical role for a high-affinity chemokine-binding protein in gamma-herpesvirus-induced lethal meningitisVictor Van Berkel
Departments of Pathology and Immunology and Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Clin Invest 109:905-14. 2002.... - Identification of the in vivo role of a viral bcl-2Shivaprakash Gangappa
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
J Exp Med 195:931-40. 2002..As gamma-herpesviruses primarily cause human disease during chronic infection, these chronic disease genes may be important targets for therapeutic intervention... - Immune control of the number and reactivation phenotype of cells latently infected with a gammaherpesvirusScott A Tibbetts
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Virol 76:7125-32. 2002..The immune system therefore controls chronic gammaherpesvirus infection by site-specific mechanisms that regulate both the number and reactivation phenotype of latently infected cells... - Antibody-independent control of gamma-herpesvirus latency via B cell induction of anti-viral T cell responsesKelly B McClellan
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri, USA
PLoS Pathog 2:e58. 2006..Exploitation of this property of B cells may allow enhanced vaccine responses to chronic virus infection... - Methylation of the EBV genome and establishment of restricted latency in low-passage EBV-infected 293 epithelial cellsEmily J Paulson
Immunology Graduate Program, Washington University School of Medicine, St. Louis, Missouri 63110, USA
Virology 299:109-21. 2002..Furthermore, these results are consistent with the hypothesis that methylation of Cp and Wp is required for entry into the type I or II latency programs... - Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infectionSharookh B Kapadia
Department of Immunology and Pathology, Department of Molecular Microbiology, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St Louis, MO 63110, USA
Immunity 17:143-55. 2002.... - Murine gammaherpesvirus 68 infection is associated with lymphoproliferative disease and lymphoma in BALB beta2 microglobulin-deficient miceVera L Tarakanova
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
J Virol 79:14668-79. 2005..Our findings suggest that gammaHV68 induces lymphomas via hit-and-run oncogenesis, paracrine effects, or stimulation of chronic inflammation... - Antibody to a lytic cycle viral protein decreases gammaherpesvirus latency in B-cell-deficient miceShivaprakash Gangappa
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110, USA
J Virol 76:11460-8. 2002..We confirmed this model by the treatment of latently infected B-cell(-/-) mice with the antiviral drug cidofovir... - An optimized CD8+ T-cell response controls productive and latent gammaherpesvirus infectionDouglas C Braaten
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, Box 8118, St. Louis, MO 63110, USA
J Virol 79:2573-83. 2005..The data also demonstrate for the first time that a strong CD8(+) T-cell response can limit long-term latent infection... - Effective vaccination against long-term gammaherpesvirus latencyScott A Tibbetts
Department of Pathology and Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
J Virol 77:2522-9. 2003..These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal... - An optimized CD4 T-cell response can control productive and latent gammaherpesvirus infectionRebecca L Sparks-Thissen
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA
J Virol 78:6827-35. 2004.... - Establishment and maintenance of gammaherpesvirus latency are independent of infective dose and route of infectionScott A Tibbetts
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
J Virol 77:7696-701. 2003..These results demonstrate that the equilibrium level of establishment of gammaherpesvirus latency is independent of the infectious dose and route of infection... - Structural basis of chemokine sequestration by a herpesvirus decoy receptorJennifer M Alexander
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
Cell 111:343-56. 2002..M3 also employs structural mimicry to promiscuously sequester chemokines, engaging conservative structural elements associated with both chemokine homodimerization and binding to G protein-coupled receptors... - EBV framed in Burkitt lymphomaSamuel H Speck
Nat Med 8:1086-7. 2002
Research Grants
- MOLECULAR MECHANISMS OF MICROBIAL PATHOGENESISSAMUEL SPECK; Fiscal Year: 2007....