Hans-Dieter Klenk

Interaction of Polymerase Subunit PB2 and NP with Importin α1 Is a Determinant of Host Range of Influenza A Virus (2008)

Gülsah Gabriel, Astrid Herwig, Hans-Dieter Klenk

We have previously reported that mutations in the polymerase proteins PB1, PB2, PA, and the nucleocapsid protein NP resulting in enhanced transcription and replication activities in mammalian cells...

Identification of a novel coronavirus in patients with severe acute respiratory syndrome. (2007)

Drosten, Christian, Günther, Stephan, Preiser, Wolfgang, Van Der Werf, Sylvie, Brodt, Hans-Reinhard, Becker, Stephan, ...

BACKGROUND: The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. METHODS: Clinical...

Identification of a novel coronavirus in patients with severe acute respiratory syndrome. (2007)

Drosten, Christian, Günther, Stephan, Preiser, Wolfgang, Van Der Werf, Sylvie, Brodt, Hans-Reinhard, Becker, Stephan, ...

BACKGROUND: The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. METHODS: Clinical...

Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses. (2006)

Szécsi, Judit, Boson, Bertrand, Johnsson, Per, Dupeyrot-Lacas, Pia, Matrosovich, Mikhail, Klenk, Hans-Dieter, ...

SUMMARY: There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles...

Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses. (2006)

Szécsi, Judit, Boson, Bertrand, Johnsson, Per, Dupeyrot-Lacas, Pia, Matrosovich, Mikhail, Klenk, Hans-Dieter, ...

SUMMARY: There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles...

Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses (2006)

Szécsi, Judit, Boson, Bertrand, Johnsson, Per, Dupeyrot-Lacas, Pia, Matrosovich, Mikhail, Klenk, Hans-Dieter, ...

Summary There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles...

New low-viscosity overlay medium for viral plaque assays (2006)

Matrosovich, Mikhail, Matrosovich, Tatyana, Garten, Wolfgang, Klenk, Hans-Dieter

Abstract Background Plaque assays in cell culture monolayers under solid or semisolid overlay media are commonly used for quantification of viruses and antiviral substances. To overcome the pitfalls...

Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses. (2006)

Szécsi, Judit, Boson, Bertrand, Johnsson, Per, Dupeyrot-Lacas, Pia, Matrosovich, Mikhail, Klenk, Hans-Dieter, ...

SUMMARY: There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles...

Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses (1998)

Jones, Steven M., Feldmann, Heinz, Stroher, Ute, Geisbert, Joan B., Fernando, Lisa, Grolla, Allen, ...

Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus...

The Ebola virus VP35 protein functions as a type I IFN antagonist

Basler, Christopher F., Wang, Xiuyan, Mühlberger, Elke, Volchkov, Victor, Paragas, Jason, Klenk, Hans-Dieter, ...

An assay has been developed that allows the identification of molecules that function as type I IFN antagonists. Using this assay, we have identified an Ebola virus-encoded inhibitor of the type I...

Processing of the Ebola virus glycoprotein by the proprotein convertase furin

Volchkov, Viktor E., Feldmann, Heinz, Volchkova, Valentina A., Klenk, Hans-Dieter

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase...

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P

Lenz, Oliver, Ter Meulen, Jan, Klenk, Hans-Dieter, Seidah, Nabil G., Garten, Wolfgang

The surface glycoprotein of the Lassa virus, a member of the arenaviridae family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and...

Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

Mühlberger, Elke, Weik, Michael, Volchkov, Viktor E., Klenk, Hans-Dieter, Becker, Stephan

The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication...

Elongation of the Cytoplasmic Tail Interferes with the Fusion Activity of Influenza Virus Hemagglutinin

Ohuchi, Masanobu, Fischer, Christian, Ohuchi, Reiko, Herwig, Astrid, Klenk, Hans-Dieter

The hemagglutinin (HA) of fowl plague virus was lengthened and shortened by site-specific mutagenesis at the cytoplasmic tail, and the effects of these modifications on HA functions were analyzed...

Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes

Mühlberger, Elke, Lötfering, Beate, Klenk, Hans-Dieter, Becker, Stephan

This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the...

Interdependence of Hemagglutinin Glycosylation and Neuraminidase as Regulators of Influenza Virus Growth: a Study by Reverse Genetics

Wagner, Ralf, Wolff, Thorsten, Herwig, Astrid, Pleschka, Stephan, Klenk, Hans-Dieter

The hemagglutinin (HA) of fowl plague virus A/FPV/Rostock/34 (H7N1) carries two N-linked oligosaccharides attached to Asn123 and Asn149 in close vicinity to the receptor-binding pocket. In previous...

Targeted Infection of Endothelial Cells by Avian Influenza Virus A/FPV/Rostock/34 (H7N1) in Chicken Embryos

Feldmann, Anke, Schäfer, Martin K.-H., Garten, Wolfgang, Klenk, Hans-Dieter

The tissue tropism and spread of infection of the highly pathogenic avian influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken embryos. As shown by in situ hybridization,...

Identification of a Novel Consensus Sequence at the Cleavage Site of the Lassa Virus Glycoprotein

Lenz, Oliver, Ter Meulen, Jan, Feldmann, Heinz, Klenk, Hans-Dieter, Garten, Wolfgang

The Lassa virus glycoprotein consists of an amino-terminal and a carboxy-terminal cleavage fragment designated GP-1 and GP-2, respectively, that are derived by proteolysis from the precursor GP-C....

Sorting of Marburg Virus Surface Protein and Virus Release Take Place at Opposite Surfaces of Infected Polarized Epithelial Cells

Sänger, Christian, Mühlberger, Elke, Ryabchikova, Elena, Kolesnikova, Larissa, Klenk, Hans-Dieter, Becker, Stephan

Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of...

A Novel Nonnucleoside Inhibitor Specifically Targets Cytomegalovirus DNA Maturation via the UL89 and UL56 Gene Products

Buerger, Iris, Reefschlaeger, Juergen, Bender, Wolfgang, Eckenberg, Peter, Popp, Andreas, Weber, Olaf, ...

3-Hydroxy-2,2-dimethyl-N-[4({[5-(dimethylamino)-1-naphthyl]sulfonyl}amino)-phenyl]propanamide (BAY 38-4766) is a novel selective nonnucleoside inhibitor of cytomegalovirus (CMV) replication with an...

Infection and Activation of Monocytes by Marburg and Ebola Viruses

Ströher, Ute, West, Elmar, Bugany, Harald, Klenk, Hans-Dieter, Schnittler, Hans-Joachim, Feldmann, Heinz

In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under...

VP40, the Matrix Protein of Marburg Virus, Is Associated with Membranes of the Late Endosomal Compartment

Kolesnikova, Larissa, Bugany, Harald, Klenk, Hans-Dieter, Becker, Stephan

Localization of VP40 in Marburg virus (MBGV)-infected cells was studied by using immunofluorescence and immunoelectron microscopic analysis. VP40 was detected in association with nucleocapsid...

Importance of the Cytoplasmic Tails of the Measles Virus Glycoproteins for Fusogenic Activity and the Generation of Recombinant Measles Viruses

Moll, Markus, Klenk, Hans-Dieter, Maisner, Andrea

The generation of replication-competent measles virus (MV) depends on the incorporation of biologically active, fusogenic glycoprotein complexes, which are required for attachment and penetration...

Ebola Virus VP30-Mediated Transcription Is Regulated by RNA Secondary Structure Formation

Weik, Michael, Modrof, Jens, Klenk, Hans-Dieter, Becker, Stephan, Mühlberger, Elke

The nucleocapsid protein VP30 of Ebola virus (EBOV), a member of the Filovirus family, is known to act as a transcription activator. By using a reconstituted minigenome system, the role of VP30...

Hantaan Virus Infection Causes an Acute Neurological Disease That Is Fatal in Adult Laboratory Mice

Wichmann, Dominic, Gröne, Hermann-Josef, Frese, Michael, Pavlovic, Jovan, Anheier, Bärbel, Haller, Otto, ...

Hantaan virus, the etiological agent of Korean hemorrhagic fever, is transmitted to humans from persistently infected mice (Apodemus agrarius), which serve as the primary reservoir. Here we...

The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Basler, Christopher F., Mikulasova, Andrea, Martinez-Sobrido, Luis, Paragas, Jason, Mühlberger, Elke, Bray, Mike, ...

The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza...

Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Matrosovich, Mikhail, Matrosovich, Tatyana, Carr, Jackie, Roberts, Noel A., Klenk, Hans-Dieter

No reliable cell culture assay is currently available for monitoring human influenza virus sensitivity to neuraminidase inhibitors (NAI). This can be explained by the observation that because of a...

Glycosphingolipids of Plasma Membranes of Cultured Cells and an Enveloped Virus (SV5) Grown in These Cells

Klenk, Hans-Dieter, Choppin, Purnell W.

Glycosphingolipids of rhesus monkey kidney (MK), bovine kidney (MDBK), and two lines of hamster kidney (BHK21-F and Hak) cells have been compared with those of parainfluenza (SV5) virions grow in...

Crystal structure of the matrix protein VP40 from Ebola virus

Dessen, Andréa, Volchkov, Viktor, Dolnik, Olga, Klenk, Hans-Dieter, Weissenhorn, Winfried

Ebola virus maturation occurs at the plasma membrane of infected cells and involves the clustering of the viral matrix protein VP40 at the assembly site as well as its interaction with the lipid...

Membrane association induces a conformational change in the Ebola virus matrix protein

Scianimanico, Sandra, Schoehn, Guy, Timmins, Joanna, Ruigrok, Rob H.W., Klenk, Hans-Dieter, Weissenhorn, Winfried

The matrix protein VP40 from Ebola virus is targeted to the plasma membrane, where it is thought to induce assembly and budding of virions through its association with the lipid bilayer. Ebola virus...

Formation of Influenza Virus Proteins

Klenk, Hans-Dieter, Rott, Rudolf

Eight virus-specific proteins have been found in chicken embryo fibroblasts infected with fowl plague virus. Among them are two glycoproteins which are the constituents of the hemagglutinin on the...

Inhibition of Glycosylation of the Influenza Virus Hemagglutinin

Schwarz, Ralph T., Klenk, Hans-Dieter

d-Glucosamine and 2-deoxy-d-glucose interfere with the biosynthesis of the hemagglutinin glycoproteins. With increasing inhibitor concentrations a progressive decrease in size of the precursor HA and...

Glycolipid Content of Vesicular Stomatitis Virus Grown in Baby Hamster Kidney Cells

Klenk, Hans-Dieter, Choppin, Purnell W.

Vesicular stomatitis virions grown in baby hamster kidney (BHK-21-F) cells were found to contain hematoside (neuraminosyl-galactosyl-glucosyl-ceramide). This ganglioside, which was the only...

Human and avian influenza viruses target different cell types in cultures of human airway epithelium

Matrosovich, Mikhail N., Matrosovich, Tatyana Y., Gray, Thomas, Roberts, Noel A., Klenk, Hans-Dieter

The recent human infections caused by H5N1, H9N2, and H7N7 avian influenza viruses highlighted the continuous threat of new pathogenic influenza viruses emerging from a natural reservoir in birds. It...

Properties of Replication-Competent Vesicular Stomatitis Virus Vectors Expressing Glycoproteins of Filoviruses and Arenaviruses

Garbutt, Michael, Liebscher, Ryan, Wahl-Jensen, Victoria, Jones, Steven, Möller, Peggy, Wagner, Ralf, ...

Replication-competent recombinant vesicular stomatitis viruses (rVSVs) expressing the type I transmembrane glycoproteins and selected soluble glycoproteins of several viral hemorrhagic fever agents...

Ectodomain shedding of the glycoprotein GP of Ebola virus

Dolnik, Olga, Volchkova, Valentina, Garten, Wolfgang, Carbonnelle, Caroline, Becker, Stephan, Kahnt, Jörg, ...

In this study, release of abundant amounts of the Ebola virus (EBOV) surface glycoprotein GP in a soluble form from virus-infected cells was investigated. We demonstrate that the mechanism...

Ubiquitous Activation of the Nipah Virus Fusion Protein Does Not Require a Basic Amino Acid at the Cleavage Site

Moll, Markus, Diederich, Sandra, Klenk, Hans-Dieter, Czub, Markus, Maisner, Andrea

Nipah virus (NiV), a highly pathogenic paramyxovirus, causes a systemic infection in vivo and is able to replicate in cultured cells of many species and organs. Such pantropic paramyxoviruses...

Carbohydrates of Influenza Virus. I. Glycopeptides Derived from Viral Glycoproteins After Labeling with Radioactive Sugars

Schwarz, Ralph T., Schmidt, Michael F. G., Anwer, Ursula, Klenk, Hans-Dieter

The carbohydrate moiety of the influenza glycoproteins NA, HA1, and HA2 were analyzed by labeling with radioactive sugars. Analysis of glycopeptides obtained after digestion with Pronase indicated...

Neuraminidase Is Important for the Initiation of Influenza Virus Infection in Human Airway Epithelium

Matrosovich, Mikhail N., Matrosovich, Tatyana Y., Gray, Thomas, Roberts, Noel A., Klenk, Hans-Dieter

Influenza virus neuraminidase (NA) plays an essential role in release and spread of progeny virions, following the intracellular viral replication cycle. To test whether NA could also facilitate...

VP24 of Marburg Virus Influences Formation of Infectious Particles

Bamberg, Sandra, Kolesnikova, Larissa, Möller, Peggy, Klenk, Hans-Dieter, Becker, Stephan

The highly pathogenic enveloped Marburg virus (MARV) is composed of seven structural proteins and the nonsegmented negative-sense viral RNA genome. Four proteins (NP, VP35, VP30, and L) make up the...

Homo-Oligomerization of Marburgvirus VP35 Is Essential for Its Function in Replication and Transcription

Möller, Peggy, Pariente, Nonia, Klenk, Hans-Dieter, Becker, Stephan

The nucleocapsid protein VP35 of Marburgvirus, a filovirus, acts as the cofactor of the viral polymerase and plays an essential role in transcription and replication of the viral RNA. VP35 forms...

Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor

Eichler, Robert, Lenz, Oliver, Strecker, Thomas, Eickmann, Markus, Klenk, Hans-Dieter, Garten, Wolfgang

Lassa virus glycoprotein is translated as a precursor (pre-GP-C) into the lumen of the endoplasmic reticulum and is cotranslationally cleaved into the signal peptide and GP-C, before GP-C is...

Rescue of Recombinant Marburg Virus from cDNA Is Dependent on Nucleocapsid Protein VP30

Enterlein, Sven, Volchkov, Viktor, Weik, Michael, Kolesnikova, Larissa, Volchkova, Valentina, Klenk, Hans-Dieter, ...

Here we report recovery of infectious Marburg virus (MARV) from a full-length cDNA clone. Compared to the wild-type virus, recombinant MARV showed no difference in terms of morphology of virus...

Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence

Kash, John C., Mühlberger, Elke, Carter, Victoria, Grosch, Melanie, Perwitasari, Olivia, Proll, Sean C., ...

We studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with Zaire Ebolavirus (ZEBOV),...

Induction of neutralising antibodies by virus-like particles harbouring surface proteins from highly pathogenic H5N1 and H7N1 influenza viruses

Szécsi, Judit, Boson, Bertrand, Johnsson, Per, Dupeyrot-Lacas, Pia, Matrosovich, Mikhail, Klenk, Hans-Dieter, ...

There is an urgent need to develop novel approaches to vaccination against the emerging, highly pathogenic avian influenza viruses. Here, we engineered influenza viral-like particles (Flu-VLPs)...

The Ebola virus VP35 protein functions as a type I IFN antagonist

Basler, Christopher F., Wang, Xiuyan, Mühlberger, Elke, Volchkov, Victor, Paragas, Jason, Klenk, Hans-Dieter, ...

An assay has been developed that allows the identification of molecules that function as type I IFN antagonists. Using this assay, we have identified an Ebola virus-encoded inhibitor of the type I...

Processing of the Ebola virus glycoprotein by the proprotein convertase furin

Volchkov, Viktor E., Feldmann, Heinz, Volchkova, Valentina A., Klenk, Hans-Dieter

In the present study, we have investigated processing and maturation of the envelope glycoprotein (GP) of Ebola virus. When GP expressed from vaccinia virus vectors was analyzed by pulse–chase...

The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P

Lenz, Oliver, Ter Meulen, Jan, Klenk, Hans-Dieter, Seidah, Nabil G., Garten, Wolfgang

The surface glycoprotein of the Lassa virus, a member of the arenaviridae family, is synthesized as a 76-kDa precursor (GP-C) that is posttranslationally cleaved into an N-terminal 44-kDa subunit and...

Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

Mühlberger, Elke, Weik, Michael, Volchkov, Viktor E., Klenk, Hans-Dieter, Becker, Stephan

The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication...

Elongation of the Cytoplasmic Tail Interferes with the Fusion Activity of Influenza Virus Hemagglutinin

Ohuchi, Masanobu, Fischer, Christian, Ohuchi, Reiko, Herwig, Astrid, Klenk, Hans-Dieter

The hemagglutinin (HA) of fowl plague virus was lengthened and shortened by site-specific mutagenesis at the cytoplasmic tail, and the effects of these modifications on HA functions were analyzed...

Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes

Mühlberger, Elke, Lötfering, Beate, Klenk, Hans-Dieter, Becker, Stephan

This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the...

Interdependence of Hemagglutinin Glycosylation and Neuraminidase as Regulators of Influenza Virus Growth: a Study by Reverse Genetics

Wagner, Ralf, Wolff, Thorsten, Herwig, Astrid, Pleschka, Stephan, Klenk, Hans-Dieter

The hemagglutinin (HA) of fowl plague virus A/FPV/Rostock/34 (H7N1) carries two N-linked oligosaccharides attached to Asn123 and Asn149 in close vicinity to the receptor-binding pocket. In previous...

Targeted Infection of Endothelial Cells by Avian Influenza Virus A/FPV/Rostock/34 (H7N1) in Chicken Embryos

Feldmann, Anke, Schäfer, Martin K.-H., Garten, Wolfgang, Klenk, Hans-Dieter

The tissue tropism and spread of infection of the highly pathogenic avian influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken embryos. As shown by in situ hybridization,...

Identification of a Novel Consensus Sequence at the Cleavage Site of the Lassa Virus Glycoprotein

Lenz, Oliver, Ter Meulen, Jan, Feldmann, Heinz, Klenk, Hans-Dieter, Garten, Wolfgang

The Lassa virus glycoprotein consists of an amino-terminal and a carboxy-terminal cleavage fragment designated GP-1 and GP-2, respectively, that are derived by proteolysis from the precursor GP-C....

Sorting of Marburg Virus Surface Protein and Virus Release Take Place at Opposite Surfaces of Infected Polarized Epithelial Cells

Sänger, Christian, Mühlberger, Elke, Ryabchikova, Elena, Kolesnikova, Larissa, Klenk, Hans-Dieter, Becker, Stephan

Marburg virus, a filovirus, causes severe hemorrhagic fever with hitherto poorly understood molecular pathogenesis. We have investigated here the vectorial transport of the surface protein GP of...

A Novel Nonnucleoside Inhibitor Specifically Targets Cytomegalovirus DNA Maturation via the UL89 and UL56 Gene Products

Buerger, Iris, Reefschlaeger, Juergen, Bender, Wolfgang, Eckenberg, Peter, Popp, Andreas, Weber, Olaf, ...

3-Hydroxy-2,2-dimethyl-N-[4({[5-(dimethylamino)-1-naphthyl]sulfonyl}amino)-phenyl]propanamide (BAY 38-4766) is a novel selective nonnucleoside inhibitor of cytomegalovirus (CMV) replication with an...

Infection and Activation of Monocytes by Marburg and Ebola Viruses

Ströher, Ute, West, Elmar, Bugany, Harald, Klenk, Hans-Dieter, Schnittler, Hans-Joachim, Feldmann, Heinz

In this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under...