Research Topics
Genomes and Genes
| Oliver T FacklerSummaryAffiliation: University of Heidelberg Country: Germany Publications
| Collaborators
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Detail Information
Publications
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...- 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... - 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.... 
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....- 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... - 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... 
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...- 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... - HIV-1 Nef compensates for disorganization of the immunological synapse by inducing trans-Golgi network-associated Lck signalingXiaoyu Pan
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Germany
Blood 119:786-97. 2012..Nef therefore hijacks Lck sorting to selectively activate TGN-associated arms of compartmentalized TCR signaling. By tailoring T-lymphocyte responses to antigenic stimulation, Nef optimizes the environment for HIV-1 replication... - 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... - 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... - 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.... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - HIV-1 Nef limits communication between linker of activated T cells and SLP-76 to reduce formation of SLP-76-signaling microclusters following TCR stimulationLibin Abraham
Department of Infectious Diseases, Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany
J Immunol 189:1898-910. 2012..Nef thus employs a dual mechanism to disturb early TCR signaling by limiting the communication between LAT and SLP-76 and preventing the dynamic formation of SLP-76-signaling MCs... - 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... - 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... - 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... - 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... - 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... - 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... - 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... - How HIV takes advantage of the cytoskeleton in entry and replicationBettina Stolp
Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany
Viruses 3:293-311. 2011..This review will recapitulate recent findings on how HIV-1 hijacks the cytoskeleton to facilitate entry into, transport within and egress from host cells as well as to commandeer communication of infected with uninfected bystander cells... - Role of the C-terminal domain of the HIV-1 glycoprotein in cell-to-cell viral transmission between T lymphocytesVanessa Emerson
Forschungsschwerpunkt Infektion und Krebs, F020, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany
Retrovirology 7:43. 2010..We aim to gain insight on the underlying requirement for the Env-CT for viral spread in non-permissive cells... - 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... - 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... - HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivoBettina Stolp
Department of Infectious Diseases Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany
Proc Natl Acad Sci U S A 109:18541-6. 2012..Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor... - 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... - 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... - 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.... - 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...