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ASSOCIATIONS
ASSOCIATIONS
Dr. Heinz Ulrich Feldmann (born 1959) ( Dr. Hans-Dieter Klenk was the mentor to Dr. Heinz Feldmann )
Dr. Purnell Whittington Choppin (born 1929) - ( [HK005G][GDrive] : "While Khans-Dieter Klenk was working on his habilitation thesis, he initially worked for three years (1967–1970) at New York's Rockefeller University as a guest investigator in [the laboratory of Dr. Purnell Whittington Choppin (born 1929)]. " )
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Hans-Dieter Klenk (born June 25, 1938 in Cologne) is a German virologist, recipient of the Robert Koch Medal, university professor and long-time director of the Institute for Virology in Marburg.
Life
Life
Klenk, the son of Ernst Klenk, studied medicine from 1958 to 1963 at the universities of Tübingen, Vienna and Cologne. In 1964 he was awarded the grade summa cum laude Dr. med. PhD. From 1964 to 1967 he completed a postgraduate course in biochemistry at the University of Tübingen. In 1971 he completed his habilitation in virology at the University of Giessen.
While he was working on his habilitation thesis, he initially worked for three years (1967–1970) at New York's Rockefeller University as a guest investigator in [the laboratory of Dr. Purnell Whittington Choppin (born 1929)]. From 1970 he was research assistant at the Institute for Medical Virology at the University of Giessen, where he worked closely with [Prof. Rudolf Rott (born 1926)] for another three years. There he was appointed C3 professor in 1973. He held this professional position for almost twelve years until he was appointed as a C4 professorship and institute director at the Philipps University of Marburg in 1985.
Hans-Dieter Klenk is married and has three adult sons.
Scientific research focus
Scientific research focus
The focus of the research that Hans-Dieter Klenk and his colleagues have dedicated themselves to are the influenza viruses as well as the Marburg and Ebola viruses. In the work, the structure and reproduction of these viruses were elucidated and important knowledge gained about the mechanisms that are responsible for the pathogenicity of the pathogens and for their transmission from animals to humans. In addition, this work formed the basis for the development of vaccines and antiviral drugs against the Ebola virus and other important pathogens.
2011-jir330.pdf
Assessment of Rodents as Animal Models for Reston Ebolavirus Emmie de Wit,1 Vincent J. Munster,1 Samia A. Metwally,2 and Heinz Feldmann1 1 Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana; 2 Food and Agriculture Organization Reference Center for Vesicular Diseases, United States Department of Agriculture, Animal and Plant Health Inspection Service, Foreign Animal Disease Diagnostic Laboratory, National Veterinary Service Laboratories, Plum Island Animal Disease Center, Greenport, New York The emergence of Reston ebolavirus (REBOV) in domestic swine in the Philippines has caused a renewed interest in REBOV pathogenicity. Here, the use of different rodent species as animal disease models for REBOV was investigated. BALB/c and STAT12/2 mice, Hartley guinea pigs, and Syrian hamsters were inoculated intraperitoneally with REBOV strain Pennsylvania or Reston08-A. Although virus replication occurred in guinea pigs, hamsters, and STAT12/2 mice, progression to disease was only observed in STAT12/2 mice. Moreover, REBOV Pennsylvania was more pathogenic than REBOV Reston08-A in this model. Thus, STAT12/2 mice may be used for research of REBOV pathogenicity and intervention strategies
[..]
The absence of disease manifestation (in BALB/c mice, Hartley guinea pigs, and Syrian hamsters) and perhaps even replication (in BALB/c mice) makes these animals interesting models as they may resemble the situation in humans, among whom REBOV-induced disease has so far not been observed. The replication of REBOV in guinea pigs and hamsters also creates the possibility of adapting REBOV to these hosts, similar to the adaptation of Zaire ebolavirus to mice and guinea pigs [13, 14], possibly resulting in a disease manifestation similar to that observed in cynomolgus macaques and thus an opportunity to study REBOV disease in guinea pigs or hamsters
[..]
refers to -
4. Volchkov VE, Chepurnov AA, Volchkova VA, Ternovoj VA, Klenk HD. Molecular characterization of guinea pig-adapted variants of Ebola virus. Virology 2000; 277:147–55
https://collections.nlm.nih.gov/catalog/nlm:nlmuid-101446451-img
2003 - Wrote obituary/memoriam for Rudolf Rott (1926-2003), with Prof. Jürgen Richt
2003 - Wrote obituary/memoriam for Rudolf Rott (1926-2003), with Prof. Jürgen Richt
Source is Virology Division News : [HP0051][GDrive] / Obituary/memoriam for Prof. Rudolf Rott (born 1926) , written with Prof. Jürgen Albrecht Richt (born 1958) .
https://www.creative-biolabs.com/vaccine/ganglioside-vaccines.htm
he name ganglioside was first applied by the German scientist Ernst Klenk in 1942 to lipids newly isolated from ganglion cells of the brain. Most gangliosides considered as potential targets for cancer therapy are expressed primarily in tissues and tumors of neuroectodermal origin
There is also evidence suggesting prions may play a part in the process of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS); these have been termed prion-like diseases.
Prof. Dr. Hans-Dieter Klenk
President of the Ernst Klenk
Foundation, Marburg
We are very pleased to announce that Prof. Adriano Aguzzi (Institute of Neuropathology, University Hospital of Zuerich, Switzerland) was substantially involved in the scientific coordination of the program. Prof. Aguzzi will also present the Ernst Klenk Lecture entitled Biology of Prion Diseases.
2011
http://www.sciforum.hu/cms/previous-fora/2011/speakers-2011/hans-dieter-klenk.html
KLENK, HANS-DIETER
Institute for Virology, University of Marburg
Hans-Dieter Klenk was born in 1938 in Cologne, Germany. He received his M.D. from the University of Cologne in 1964 and a degree in biochemistry from the University of Tübingen in 1967. From 1967 to 1970 he was a postdoctoral fellow with Dr. P.W. Choppin at the Rockefeller University in New York. From 1970 to 1985 he held several positions at the Institute of Virology of the University of Giessen. From 1985 to 2007 he was Professor of Virology and Head of the Department of Virology of the University of Marburg where he is now Professor emeritus. His research has focused on the structure and function of enveloped viruses (influenza viruses, paramyxoviruses, filoviruses) with special emphasis on the role of viral glycoproteins and RNA polymerase in the infection process, in pathogenesis and in interspezies transmission. He is author of more than 400 scientific publications. Prof. Klenk was President of the Gesellschaft für Virologie and Chairman of the Virology Division of the International Union of Microbiological Societies. He serves presently on the International Scientific Board of the Institute of Medical Microbiology of Fudan University, Shanghai, on the Scientific Advisory Board of the Pasteur Institute of the Chinese Academy of Science, Shanghai, on the International Scientific Board of the Guangzhou Institute of Biomedicine and Health of the Chinese Academy of Science, and of the Influenza Pathogenesis and Immunology Research Center, Atlanta. He is a member of EMBO and of the Deutsche Akademie der Naturforscher, Leopoldina. His awards include: Preis der Deutschen Gesellschaft für Hygiene und Mikrobiologie (1985), Feldberg Lecture, London (1987), Aronson-Preis, Berlin (1989), Shipley Lecture, Harvard Medical School (2003), Robert-Koch-Medal in Gold, Berlin (2006), Ernst-Jung-Medal in Gold, Hamburg (2008), Emil von Behring-Preis, Marburg (2010).
NOTES - "University of Giessen" is only 5 miles from Marburg
https://en.wikipedia.org/wiki/Purnell_W._Choppin
Purnell W. Choppin is an American virologist. He served on the faculty of Rockefeller University for nearly thirty years, becoming the Leon Hess Professor of Virology. He moved to the Howard Hughes Medical Institute in 1985, became the president of the institute in 1987, and retired in 1999, succeeded by Thomas Cech. He is currently the chair of the Scientific Advisory Board at the Center for the Study of Hepatitis C, supported by a university consortium consisting of Rockefeller, Weill Cornell Medical College, and New York-Presbyterian Hospital.[1][2]
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In 1985 Choppin moved from his position as the Leon Hess Professor of Virology at Rockefeller to the Howard Hughes Medical Institute, where he served as vice president and chief scientific officer. He assumed the presidency in 1987, succeeding Donald Fredrickson.[4]
Appendix CNational Institutes of Health Aids Program Advisory Committee
Appendix CNational Institutes of Health Aids Program Advisory Committee
Martin S. Hirsch (chair), Professor of Medicine, Harvard Medical School, Boston, Massachusetts
Baruj Benacerraf, Fabyan Professor of Comparative Pathology and Chairman, Department of Pathology, Harvard Medical School, Boston, Massachusetts
Dani Paul Bolognesi, James B. Duke Professor, Department of Surgery, Surgical Virology Laboratory, Duke University Medical Center, Durham, North Carolina
Purnell W. Choppin, President, Howard Hughes Medical Institute, Bethesda, Maryland
Evan M. Hersh, Chief, Section of Hematology and Oncology, Arizona Cancer Center, University of Arizona, Tucson
Robert J. Levine, Professor, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut
Thomas E. Malone, Vice President, Division of Biomedical Research, Association of American Medical Colleges, Washington, D.C.
Wendy K. Mariner, Professor of Law and Public Health, Boston University School of Public Health, Boston, Massachusetts
William Raub, Acting Director, National Institutes of Health, Bethesda, Maryland
Gary R. Smith, Professor, School of Law, Emory University, Atlanta, Georgia
Jose Szapocznik, Research Professor, Department of Psychiatry, University of Miami
Diane W. Wara, Professor of Pediatrics, School of Medicine, University of California, San Francisco
Constance B. Wofsy, Co-director, AIDS Activities Division, and Assistant Chief, Infectious Diseases, San Francisco General Hospital
Anthony S. Fauci (executive secretary), Director, Office of AIDS Research, and Director, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland
Dr. Anthony Fauci NIAID, NIH 1985 Acquired Immunodeficiency Syndrome: Update Dr. Anthony Cerami Rockefeller University 1986 Cytokines and Human Disease
https://en.wikipedia.org/wiki/Rockefeller_University
The Rockefeller University was founded in June 1901 as The Rockefeller Institute for Medical Research—often called simply The Rockefeller Institute—by John D. Rockefeller, who had founded the University of Chicago in 1889, upon advice by his adviser Frederick T. Gates[1] and action taken in March 1901 by his son, John D. Rockefeller Jr.[7] Greatly elevating the prestige of American science and medicine, it was America's first biomedical institute, like France's Pasteur Institute (1888) and Germany's Robert Koch Institute (1891).[1] The Rockefeller Foundation, a philanthropic organization, founded in 1913, is a separate entity, but had close connections mediated by prominent figures holding dual positions.[8]
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Notable individuals
Notable individuals
Notable figures to emerge from the institution include Alexis Carrel, Peyton Rous, Hideyo Noguchi, Thomas Milton Rivers, Richard Shope, Thomas Francis Jr, Oswald T. Avery, Rebecca Lancefield, Wendell Meredith Stanley, René Dubos, Ashton Carter, and Cornelius P. Rhoads. Others attained eminence before being drawn to the university. Joshua Lederberg, who won the Nobel Prize in Physiology or Medicine in 1958, served as president of the university from 1978 to 1990.[12] Paul Nurse, who won the Nobel Prize in Physiology or Medicine in 2001, was president from 2003 to 2010.[13] (Before Nurse's tenure, Thomas Sakmar was acting-president from 2002.[14]) In all, as of October 2020, 38 Nobel Prize recipients have been associated with the University. In the mid-1970s, the University attracted a few prominent academicians in the humanities, such as Saul Kripke.
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well well - look at this 1994 book
Preston, Richard (1994). The Hot Zone. New York: Random House. p. 300. ISBN 978-0679437840
http://1.droppdf.com/files/fr1vP/the-hot-zone-richard-preston.pdf
https://ia601202.us.archive.org/24/items/THEHOTZONE/THE_HOT_ZONE_Richard_Preston.pdf
'Lessons to be learned from the ebolavirus outbreak in West Africa
August 2014
DOI: 10.1038/emi.2014.68 '
1977, from the book The Influenza Virus Hemagglutinin Symposium, Baden near Vienna, March 21-23, 1977 : "Activation of Influenza Virus Infectivity by Proteolytic Cleavage of the Hemagglutinin"
1977, from the book The Influenza Virus Hemagglutinin Symposium, Baden near Vienna, March 21-23, 1977 : "Activation of Influenza Virus Infectivity by Proteolytic Cleavage of the Hemagglutinin"
Source PDF of full book of the Symposium : [HI002H][GDrive] / PDF of this article only (pg 69-81): [HI002I][GDrive]
Authors :
Abstract
Abstract
"It is reasonable to assume that a virus disease is manifest in a clinical sense, if cells of vital functional significance are infected by the virus and are killed or at least modified by this infection. Since the tropism of a virus for a host cell represents primarily an interaction between the surface components of the virus and receptors of the cell it is appealing to postulate that structures of a virus surface might determine the infectivity and pathogenic properties of the virus. The results of our experiments have to be interpreted in this sense, because we could demonstrate such an inter-relationship for the hemagglutinin of influenza virus."
ACTIVATION OF INFLUENZA VIRUS INFECTIVITY BY PROTEOLYTIC CLEAVAGE OF THE HEMAGGLUTININ
ACTIVATION OF INFLUENZA VIRUS INFECTIVITY BY PROTEOLYTIC CLEAVAGE OF THE HEMAGGLUTININ
It is reasonable to assume that a virus disease is manifest in a clinical sense, if cells of vital functional significance are infected by the virus and are killed or at least modified by this infection. Since the tropism of a virus for a host cell represents primarily an interaction between the surface components of the virus and receptors of the cell it is appealing to postulate that structures of a virus surface might determine the infectivity and pathogenic properties of the virus. The results of our experiments have to be interpreted in this sense, because we could demonstrate such an inter-relationship for the hemagglutinin of influenza virus.
The hemagglutinin is synthesized on the rough endoplasmic reticulum and migrates via the smooth membranes to the plasma membrane. During this transport along membraneous structures the hemagglutinin is glycosylated to form a precursor hemagglutinin (HA) with a molecular weight of 75,000. This structure is cleaved into two smaller products, HA 1 and HA2, which are held together by disulfide bonds (for reference see Rott and Klenk, 1977). Cleavage may take place either on smooth internal membranes (Klenk eta!., 1974) or at the plasma membrane (Lazarowitz eta!., 1971 ). The proteolytic nature of the cleavage reaction has been verified by the observation that in vitro incubation of virions with trypsin results in a conversion of HA to HA 1 and HA2 (Lazarowitz et at., 1973) and that cleavage of HA in vivo can be blocked by a protease inhibitor (Klenk and Rott, 1973).
Proteolytic cleavage is not necessary for the formation of intact virus particles and for their liberation from the host cell. Under certain circumstances virus particles which still contain an uncleaved HA can be released from the host cell.
Particles with a precursor HA or the hemagglutinin composed of the cleavage products HA 1 and HA2 are equally capable of a hemagglutination reaction, and in both cases the hemagglutination can be inhibited by specific antisera. This means that the reactive antigenic determinant is not significantly modified by proteolytic cleavage. The same holds true for the interaction of the hemagglutinin with the host cell. In all systems tested cleavage was not necessary to establish adsorption of virus particles to neuraminic acid containing receptors at the cell surface. A cleaved HA is necessary, however, for the infectious process to proceed further (Klenk eta/., 1975; Lazarowitz and Choppin, 1975).
Infection of embryonated chicken eggs or cells derived from the chorioallantoic membrane of the chick embryo with influenza strains of human and animal origin results in the formation of infectious progeny virus. Attempts to grow infectious viruses in chick fibroblasts are only successful with strains which possess the hema.gglutinin of fowl plague virus (FPV), while all others have only a negligible infectivity. Analyses in polyacrylamide gels show a direct correlation between infectivity and the structure of the hemagglutinin. Only particles with a cleaved HA are infectious. A successful cleavage of HA which corresponds to productive conditions in vivo can be carried out in vitro by treating the inactive virus particles with trypsin. Such a treatment also activates infectivity (Table 1 ).
A productive infection of cells in which infectious virus is normally not formed is attained if trypsin is added to the culture medium. This becomes particularly evident, if cells are infected under single and multiple cycle conditions with a multiplicity of infection ranging from 30 to 0.003 PFU/cell (Figure 1 ). Growth curves of FPV which is synthesized in such cells as infectious particles with cleaved HA are identical irrespective of the presence of trypsin. On the other hand a clear requirement for the enzyme is observed in the case of virus N.
When trypsin is present in the medium, replication is similar to that of FPV. In the absence of trypsin, however, newly synthesized non-infectious virus is only demonstrable under single cycle conditions. Under multiple cycle conditions virus production progressively decreases as the multiplicity of infection is reduced. This phenomenon also explains plaque formation by such strains which are normally non-plaque producers in chick fibroblasts in the presence of trypsin (Figure 2).
Whether a proteolytic cleavage is possible in a given host cell is determined primarily by the individual structural characteristics of the HA rather than by the activation of cellular proteases by the infecting virus. This could be demonstrated by double infection of chicken fibroblasts with FPV and virus N, which are produced in highly infectious form or with reduced infectivity, respectively.
Since HA 1 and HA 2 have different electrophoretic mobilities in FPV and virus N, it was possible to determine the origin of the cleaved HA in the mixed virus population by coelectrophoresis with homogeneous preparations of each virus.
The glycoprotein pattern of the progeny virus is shown in Figure 3. The results show clearly that after double infection FPV does not induce cleavage of the hemagglutinin glycoprotein of virus N. Biological tests confirm our previous observation that virus N requires try;>sin to undergo multiple cycle replication in chick fibroblasts, whereas FPV can do so in the absence of the enzyme. In doubly infected cells only FPV-specific hemagglutinin is formed if trypsin is absent. In the presence of trypsin, however, hemagglutinin of both strains can be detected (Table 2).
[...]
Comparisons of the nuclear magnetic resonance (NMR) spectra of chicken fibroblasts exposed to virus N with either cleaved or uncleaved HA are being carried out in our laboratory by C. Nicolau and H-D. Klenk. The results suggest that the hemagglutinin is in fact involved in the penetration process. These studies indicate that virus N with cleaved HA induces an alteration in the fluidity of the lipid bilayer of the plasma membrane, whereas virus N containing uncleaved HA does not. Simitar but more distinct fluidity changes have been observed when Newcastle disease virus containing a biologically active fusion glycoprotein has been compared to virus containing an inactive F glycoprotein.
This could mean that the mechanisms of penetration process resemble each other in both cases and that the function, which is exerted by the F glycoprotein of paramyxoviruses must be attributed to the hemagglutinin of influenza viruses.
Since a hemagglutinin composed of the cleavage products of HA 1 and HA2 is indispensable for the formation of infectious virus particles, only those conditions which have been def"med in our in vitro studies can predispose to a pathological situation in the host organism. In contrast to former conclusions from others it is now clear, however, that viral glycoproteins alone do not determine pathogenicity of influenza viruses. This could be convincingly deduced from a series of experiments, where recombinants of fowl plague virus were compared in vitro and in vivo (Rott et al., 1976). In these experiments there was no correlation between the presence of cleaved glycoproteins and the pathogenicity of the virus. Furthermore, using the same parent recombinants for double infection, the progeny back recombinants were only infrequently pathogenic for chicken, although they carried both surface antigens of the highly pathogenic FPV (Table 5). The results of these experiments show clearly that the pathogenicity of influenza virus depends on more than one gene. This conclusion was underlined by experiments (Table 6) where FPV recombinants were employed which carried a particular defined gene from other influenza viruses (Scholtissek et al., 1977). Here again it became clear that the FPV derived HA cannot induce the disease in the natural host, but a certain gene constellation is necessary to make up a pathogenic virus. Full reconstitution of pathogenicity to levels of the wild type FPV largely depends on the parent strain being used for the gene exchange and the particular gene which is carried 0'Ä~er. This means again that there is no individual gene coding for pathogenicity and that the HA gene is not a 'virulence' gene by itself.
At the present time we cannot list the optimal gene constellation to make up a pathogenic virus and we are not in a position yet to define the particular contribution made by the individual genes which might finally result in the complex phenomenon of pathogenicity.
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