Research Topics
Genomes and Genes
| Oliver T FacklerSummaryAffiliation: University of Heidelberg Country: Germany Publications
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Detail Information
Publications
Modulation of the immunological synapse: a key to HIV-1 pathogenesis?Oliver T Fackler
Oliver T Fackler is at the Department of Virology, University of Heidelberg, D 69120 Heidelberg, Germany
Nat Rev Immunol 7:310-7. 2007..We propose that modulating lymphocyte signalling, apoptosis and intracellular trafficking ensures efficient spread of the virus in the hostile environment of the immune system...- Interactions of human retroviruses with the host cell cytoskeletonOliver T Fackler
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
Curr Opin Microbiol 9:409-15. 2006..Exciting progress has been made in understanding how HIV and HTLV polarize actin and also control microtubule organization to spread from donor to target cells in close cell-contacts termed virological synapses... - Functional characterization of HIV-1 Nef mutants in the context of viral infectionOliver T Fackler
Department of Virology, University of Heidelberg, INF 324, D 69120 Heidelberg, Germany
Virology 351:322-39. 2006..The results emphasize that multiple activities govern Nef's effects on HIV replication and argue against a role of virion incorporation for Nef's activity as pathogenicity factor... - Modulation of specific surface receptors and activation sensitization in primary resting CD4+ T lymphocytes by the Nef protein of HIV-1Oliver T Keppler
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Leukoc Biol 79:616-27. 2006..Our data support the involvement of modulation of a defined set of cell surface receptors and sensitization to activation rather than an autonomous activation function in the role of Nef in HIV-1 pathogenesis... 
Expression of Nef downregulates CXCR4, the major coreceptor of human immunodeficiency virus, from the surfaces of target cells and thereby enhances resistance to superinfectionStephanie Venzke
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
J Virol 80:11141-52. 2006..The downregulation of chemokine coreceptors is a conserved activity of Nef to modulate infected cells, an important functional consequence of which is an enhanced resistance to HIV superinfection...- Specific and distinct determinants mediate membrane binding and lipid raft incorporation of HIV-1(SF2) NefSimone I Giese
Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
Virology 355:175-91. 2006.... - The HIV-1 pathogenicity factor Nef interferes with maturation of stimulatory T-lymphocyte contacts by modulation of N-Wasp activityClaudia Haller
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Biol Chem 281:19618-30. 2006..Together, our results demonstrate that Nef alters both the amount and composition of signaling microclusters. We propose modulation of actin dynamics as an important mechanism for Nef-induced alterations of TCR signaling... - The Nef protein of human immunodeficiency virus is a broad-spectrum modulator of chemokine receptor cell surface levels that acts independently of classical motifs for receptor endocytosis and Galphai signalingNico Michel
Department of Virology, University of Heidelberg, D 69120 Heidelberg, Germany
Mol Biol Cell 17:3578-90. 2006..Nef uses a mechanism that is distinct from well-established pathways orchestrating CKR metabolism and offers an interesting tool to study the multifaceted biology of CKRs... - Lentiviral Nef proteins utilize PAK2-mediated deregulation of cofilin as a general strategy to interfere with actin remodelingBettina Stolp
Department of Infectious Diseases, Virology, University of Heidelberg, INF 324, 69120 Heidelberg, Germany
J Virol 84:3935-48. 2010.... 
The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbingSebastian Hannemann
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
J Biol Chem 283:27891-903. 2008..These results define a role for endogenous FHOD1 in SH4 domain-induced blebbing and suggest that its activity is regulated by ROCK1 in a Src-dependent manner...- The Nef protein of human immunodeficiency virus establishes superinfection immunity by a dual strategy to downregulate cell-surface CCR5 and CD4Nico Michel
Department of Virology, University of Heidelberg, Germany
Curr Biol 15:714-23. 2005..This state of superinfection immunity counteracts potentially detrimental consequences for the infected cell and facilitates high-level replication and viral spread in the host... - Antagonism of CD317 restriction of human immunodeficiency virus type 1 (HIV-1) particle release and depletion of CD317 are separable activities of HIV-1 VpuChristine Goffinet
Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Virol 84:4089-94. 2010..Thus, Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation... - HIV-1 Vpu's lipid raft association is dispensable for counteraction of the particle release restriction imposed by CD317/TetherinJoëlle V Fritz
Department of Infectious Diseases, Virology, University of Heidelberg, INF 324, 69120 Heidelberg, Germany
Virology 424:33-44. 2012..We conclude that (i) lipid raft incorporation is dispensable for Vpu-mediated CD317 antagonism and (ii) Vpu does not antagonize CD317 by extraction from lipid rafts... - β-TrCP is dispensable for Vpu's ability to overcome the CD317/Tetherin-imposed restriction to HIV-1 releaseHanna Mari Tervo
Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany
Retrovirology 8:9. 2011..Recently, it has been suggested that β-TrCP is also critically involved in Vpu's ability to overcome the CD317-mediated virion release block... - Determinants in HIV-1 Nef for enhancement of virus replication and depletion of CD4+ T lymphocytes in human lymphoid tissue ex vivoStefanie Homann
Department of Virology, University of Heidelberg, Germany
Retrovirology 6:6. 2009.... - Differing and isoform-specific roles for the formin DIAPH3 in plasma membrane blebbing and filopodia formationJana Stastna
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany
Cell Res 22:728-45. 2012..We propose that isoform-selective actin assembly by DIAPH3 exerts specific and differentially regulated functions during cell adhesion and motility... - Nef does not inhibit F-actin remodelling and HIV-1 cell-cell transmission at the T lymphocyte virological synapseClaudia Haller
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany
Eur J Cell Biol 90:913-21. 2011..Nef therefore selectively interferes with actin remodelling processes involved in antiviral host cell defense while actin driven processes that promote virus propagation remain unaltered... - Human immunodeficiency virus type 1 Nef activates p21-activated kinase via recruitment into lipid raftsEllen Krautkrämer
Abteilung Virologie, Universitatsklinikum Heidelberg, D 69120 Heidelberg, Germany
J Virol 78:4085-97. 2004..Together, these data suggest that Nef induces signal transduction via the recruitment of a signaling machinery including Pak into lipid rafts, thereby mimicking a physiological cellular mechanism to initiate the TCR cascade... - HIV-1 Nef interferes with host cell motility by deregulation of CofilinBettina Stolp
Department of Virology, Im Neuenheimer Feld 324, University of Heidelberg, Heidelberg 69120, Germany
Cell Host Microbe 6:174-86. 2009..We conclude that HIV-1 Nef alters Pak2 function, which directly or indirectly inactivates cofilin, thereby restricting migration of infected T lymphocytes as part of a strategy to optimize immune evasion and HIV-1 replication... - FHOD1 coordinates actin filament and microtubule alignment to mediate cell elongationJudith E Gasteier
Abteilung Virologie, Universitatsklinikum Heidelberg, INF 324, D 69120 Heidelberg, Germany
Exp Cell Res 306:192-202. 2005..Thus, sustained cell elongation was a consequence of FHOD1-mediated actin-microtubule coordination. These results suggest filament coordination as a conserved function of mammalian DRFs... - HIV-1 Vpu blocks recycling and biosynthetic transport of the intrinsic immunity factor CD317/tetherin to overcome the virion release restrictionSarah Schmidt
Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany
MBio 2:e00036-11. 2011..This describes a novel mechanism of immune evasion by HIV... - Inhibition of T-cell receptor-induced actin remodeling and relocalization of Lck are evolutionarily conserved activities of lentiviral Nef proteinsJochen M Rudolph
Department of Virology, University of Heidelberg, INF 324, 69120 Heidelberg, Germany
J Virol 83:11528-39. 2009..These results establish alterations of early TCR signaling events at the IS, including F-actin remodeling and relocalization of Lck, as evolutionary conserved activities of highly divergent lentiviral Nef proteins... - Human immunodeficiency virus type 1 Nef recruits the guanine exchange factor Vav1 via an unexpected interface into plasma membrane microdomains for association with p21-activated kinase 2 activitySusanne Rauch
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Virol 82:2918-29. 2008..These results identify Vav1 as a relevant component of the Nef-PAK2 signalosome and provide a molecular basis for the role of F195 in formation of a catalytically active Nef-PAK2 complex... - HIV-1 at the immunological and T-lymphocytic virological synapseClaudia Haller
Department of Virology, University of Heidelberg, INF 324, D 69120 Heidelberg, Germany
Biol Chem 389:1253-60. 2008..The careful dissection of these opposing effects will contribute to our understanding of retroviral spread and cellular signal transduction machineries... - SAMHD1 restricts HIV-1 infection in resting CD4(+) T cellsHanna Mari Baldauf
Department of Infectious Diseases, Virology, University of Heidelberg, Heidelberg, Germany
Nat Med 18:1682-7. 2012..Together, these findings may unveil new ways to interfere with the immune evasion and T cell immunopathology of pandemic HIV-1... - Involvement of clathrin-mediated endocytosis in human immunodeficiency virus type 1 entryJessica Daecke
Abteilung Virologie, , Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany
J Virol 79:1581-94. 2005..We conclude that dynamin-dependent, clathrin-mediated endocytosis can lead to productive entry of HIV in HeLa cells, suggesting this pathway as an alternative route of virus entry... - Rodent cells support key functions of the human immunodeficiency virus type 1 pathogenicity factor NefOliver T Keppler
Department of Virology, University of Heidelberg, Im Neuenheimer Feld 324, D 69120 Heidelberg, Germany
J Virol 79:1655-65. 2005.... - HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factorChristine Goffinet
Department of Virology, University of Heidelberg, Heidelberg, Germany
Cell Host Microbe 5:285-97. 2009..Thus, HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells, and the species-specific resistance to this suppression may guide the development of small animal models of HIV infection... - Human immunodeficiency virus type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomainsBritta Brugger
Heidelberg University Biochemistry Center BZH, Heidelberg, Germany
Retrovirology 4:70. 2007..Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition... - Human endogenous retrovirus HERV-K(HML-2) encodes a stable signal peptide with biological properties distinct from RecAlessia Ruggieri
Department of Human Genetics, Medical Faculty, University of Saarland, Homburg, Germany
Retrovirology 6:17. 2009..The human endogenous retrovirus HERV-K(HML-2) family is associated with testicular germ cell tumors (GCT). Various HML-2 proviruses encode viral proteins such as Env and Rec... - Cell motility through plasma membrane blebbingOliver T Fackler
Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
J Cell Biol 181:879-84. 2008..The importance of blebbing as a functional protrusion is underscored by the existence of multiple molecular mechanisms that govern actin-mediated bleb retraction... - Live and let die: Nef functions beyond HIV replicationOliver T Fackler
Department of Virology, University of Heidelberg, D-69120 Heidelberg, Germany
Immunity 16:493-7. 2002..By targeting the T cell receptor, Nef may not only prime viral replication but, more importantly, ensure viral survival through distinct mechanisms of immune evasion and antiapoptosis... - HIV-1 Nef: a multifaceted modulator of T cell receptor signalingLibin Abraham
Department of Infectious Diseases, Virology, University Hospital Heidelberg, INF 324, Heidelberg, 69120, Germany
Cell Commun Signal 10:39. 2012..We also discuss the implications of these alterations in the context of HIV-1 infection and in light of current concepts of TCR signal transduction... - Activation of the Rac-binding partner FHOD1 induces actin stress fibers via a ROCK-dependent mechanismJudith E Gasteier
Institute for Hygiene, Department of Virology, University of Heidelberg, 69120 Heidelberg, Germany
J Biol Chem 278:38902-12. 2003..These results indicate that FHOD1 acts as an effector of Rac in actin rearrangements and transcriptional regulation and may provide a link for the Rac-dependent activation of the Rho cascade... - Positive feedback between Dia1, LARG, and RhoA regulates cell morphology and invasionThomas M Kitzing
Institute of Pharmacology, University of Heidelberg, 69120 Heidelberg, Germany
Genes Dev 21:1478-83. 2007..Our results reveal that Dia1 is necessary for LPA-stimulated Rho/ROCK signaling and bleb-associated cancer cell invasion. Thus, Dia1-dependent RhoA activation constitutes a positive feedback mechanism to modulate cell behavior... - Novel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targetingDietlinde Wolf
University of Miami, Miller School of Medicine, Department of Microbiology and Immunology, BCRI 739, Miami, FL 33136, USA
Virology 370:45-54. 2008..We conclude that the activation of nPKCs by Nef is required to increase viral replication/infectivity and direct the subcellular localization of Nef... - SH4-domain-induced plasma membrane dynamization promotes bleb-associated cell motilityStella Tournaviti
Heidelberg University Biochemistry Center, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany
J Cell Sci 120:3820-9. 2007.... - Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machineryMatthias Geyer
Department of Medicine, University of California, San Francisco, California 94143 0703, USA
J Biol Chem 277:28521-9. 2002..Finally, blocking the expression of V1H decreased the enhancement of virion infectivity by Nef. Thus, V1H can function as an adaptor for interactions between Nef and AP-2... - HIV-1 Nef employs two distinct mechanisms to modulate Lck subcellular localization and TCR induced actin remodelingClaudia Haller
Abteilung Virologie, Universitatsklinikum Heidelberg, Heidelberg, Germany
PLoS ONE 2:e1212. 2007..Thus, Nef affects IS function via multiple independent mechanisms to optimize virus replication in the infected host... - Nef binds p6* in GagPol during replication of human immunodeficiency virus type 1Luciana J Costa
Department of Medicine, University of California San Francisco, UCSF Mt Zion Cancer Center, 2340 Sutter Street, San Francisco, CA 94115, USA
J Virol 78:5311-23. 2004..Our data demonstrate that the retention of Nef in the intermediate compartment interferes with viral replication and suggest a new role for Nef in the production of HIV-1... - Construction and characterization of an HIV-1 group O infectious molecular clone and analysis of vpr- and nef-negative derivativesDenis M Tebit
Abteilung Virologie, , D-69ab0, Germany
Virology 326:329-39. 2004..5. Virus obtained from pCMO2.5 replicated with similar kinetics as the parental O-type isolate in both PBMC and MDM, making this proviral clone a valuable tool for further studies on functional characteristics of HIV-1 group O viruses... - Construction and characterization of a fluorescently labeled infectious human immunodeficiency virus type 1 derivativeBarbara Muller
Abteilung Virologie, Universitätklinikum Heidelberg, Germany
J Virol 78:10803-13. 2004..The fluorescent virus derivative is a useful tool for investigating the interaction of HIV with live cells... - Replication of M-tropic HIV-1 in activated human intestinal lamina propria lymphocytes is the main reason for increased virus load in the intestinal mucosaSheriff Aziz
Internal Medicine II, University Saarland, Homburg/Saar, Germany
J Acquir Immune Defic Syndr 38:23-30. 2005..Thus, the elevated activation state of target cells in the intestine and not the expression of the homing marker CD103 is directly linked to massive HIV production... - CTL-mediated selective pressure influences dynamic evolution and pathogenic functions of HIV-1 NefTakamasa Ueno
Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Kumamoto, Japan
J Immunol 180:1107-16. 2008..These results highlight CTL immunosurveillance as important modulators of Nef's biological activity in the infected host... - The Pro78 residue regulates the capacity of the human immunodeficiency virus type 1 Nef protein to inhibit recycling of major histocompatibility complex class I molecules in an SH3-independent mannerNicoletta Casartelli
Division of Immunology and Infectious Disease, Children s Hospital Bambino Gesu, Piazza S Onofrio 4, 00165 Rome, Italy
J Gen Virol 87:2291-6. 2006..In addition, it is demonstrated that P72 and P75, and thus the SH3-binding capacity, are fully dispensable for Nef activity on MHC-I... - Subunit H of the V-ATPase involved in endocytosis shows homology to beta-adaptinsMatthias Geyer
Howard Hughes Medical Institute, Department of Medicine, University of California at San Francisco, California 94143 0703, USA
Mol Biol Cell 13:2045-56. 2002..Based on recent structural analysis, our results suggest that the di-leucine-binding domain consists of a HEAT or ARM repeat protein fold... - Biochemical characterization of the diaphanous autoregulatory interaction in the formin homology protein FHOD1André Schönichen
Max Planck Institute for Molecular Physiology, Department of Physical Biochemistry, D 44227 Dortmund, Germany
J Biol Chem 281:5084-93. 2006....