Forum für Wissenschaft, Industrie und Wirtschaft

Hauptsponsoren:     3M 
Datenbankrecherche:

 

Herpes viruses in action

22.05.2015

How herpes viruses bring the molecular biology of human cells into disarray: Scientists from Würzburg, Cambridge, and Munich present new findings in “Nature Communications”, casting doubt on previous knowledge in the field.

When a cold is coming on, many people notice that their lips start to itch. The reason for this is herpes simplex virus 1 (HSV-1). While the common cold sores are relatively harmless, the virus can also cause life-threatening disease. In intensive care units, for example, the virus commonly leads to severe lung infections. In healthy people, it can spontaneously cause inflammation of the brain, which regularly triggers irreversible brain damage.

The genetic material of the virus consists of DNA, like in humans. As soon as HSV-1 has penetrated into human cells, it smuggles its genome into the cell nucleus. This is where the molecular machinery is located that is used to read the genetic information of the DNA and to transcribe it into RNA molecules. This RNA then determines which proteins are produced by the cell.

In the cell nucleus, the virus takes full control of this machinery within a few hours of infection. It uses it to produce its own proteins and produce new virus particles on a massive scale. Formation of the cellular proteins soon becomes almost an irrelevance. In the end, the host cell dies off and thousands of new viruses are released that again infect other cells.

Reading of human DNA is disrupted

Virologists under Professor Lars Dölken who recently joined the University of Würzburg from the University of Cambridge (UK) are now presenting new details of this process in collaboration with the bioinformatics team led by Professor Caroline Friedel (LMU Munich). Their work has been published in the journal “Nature Communications”.

The researchers used cell cultures to comprehensively analyze the course of HSV-1 infection of human connective tissue cells (fibroblasts) and examine what happens with all the RNA molecules in the cells during the process. They used a new approach quantifying RNA synthesis, processing and translation in a single experimental setting using high-throughput sequencing.

As quickly as three to four hours after virus entry, the scientists observed a completely unexpected effect: The process of transcribing human DNA into RNA no longer stopped at the appropriate sites at the end of genes but simply carried on for tens-of-thousands of nucleotides and often across several neighboring genes. This creates masses of unusable RNA products that can no longer properly translate into proteins.

Interestingly, the viral DNA continued to be accurately transcribed throughout infection. Selectively interfering with transcription termination of cellular genes is of direct benefit to the virus. It enforces shut-off of the cell thereby interfering with any arising antiviral host response. In addition, it increases the synthesis of viral proteins and thus aids the production of new virus particles.

Hundreds of genes are aroused, but remain silent

The newly discovered mechanism can give the impression that the virus also activates a large number of genes in the cell, but this is actually not the case. “It is likely that experimental data was falsely interpreted in the past,” is the conclusion drawn by the researchers. According to their findings, hundreds of cellular genes seemingly activated by the viruses are not translated into proteins at all. “Unlike previous studies which only studied single genes, we also found no indication that the virus generally impedes the processing of RNA in the cell nucleus, known as splicing,” says Dölken. Instead, it causes unusual splicing events, many of which have never before been observed.

The research team from Würzburg, Cambridge, and Munich set a milestone in methodology with this work: With a single experimental approach it is possible to record all the changes that occur when transcribing and processing RNA as well as their impact on protein production.

Wide-spread disruption of host transcription termination in HSV-1 infection, Andrzej J. Rutkowski, Florian Erhard, Anne L’Hernault, Thomas Bonfert, Markus Schilhabel, Colin Crump, Philip Rosenstiel, Stacey Efstathiou, Ralf Zimmer, Caroline C. Friedel, Lars Dölken. Nature Communications, 20th May 2015, DOI: 10.1038/ncomms8126

Contact

Prof. Dr. Lars Dölken, Institute of Virology and Immunobiology, Julius Maximilian University of Würzburg, T +49 (0)931 31-88185, lars.doelken@vim.uni-wuerzburg.de

Prof. Dr. Caroline Friedel, Institute for Informatics (Bioinformatics), Ludwig Maximilian University of Munich, T +49 (0)89 2180-4056, Caroline.Friedel@bio.ifi.lmu.de

Robert Emmerich | Julius-Maximilians-Universität Würzburg
Weitere Informationen:
http://www.uni-wuerzburg.de

Weitere Nachrichten aus der Kategorie Biowissenschaften Chemie:

nachricht Geteiltes Denken ist doppeltes Denken
19.01.2017 | Hertie-Institut für klinische Hirnforschung (HIH)

nachricht Neue CRISPR-Methode enthüllt Genregulation einzelner Zellen
19.01.2017 | CeMM Forschungszentrum für Molekulare Medizin der Österreichischen Akademie der Wissenschaften

Alle Nachrichten aus der Kategorie: Biowissenschaften Chemie >>>

Die aktuellsten Pressemeldungen zum Suchbegriff Innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Verkehrsstau im Nichts

Konstanzer Physiker verbuchen neue Erfolge bei der Vermessung des Quanten-Vakuums

An der Universität Konstanz ist ein weiterer bedeutender Schritt hin zu einem völlig neuen experimentellen Zugang zur Quantenphysik gelungen. Das Team um Prof....

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: Textiler Hochwasserschutz erhöht Sicherheit

Wissenschaftler der TU Chemnitz präsentieren im Februar und März 2017 ein neues temporäres System zum Schutz gegen Hochwasser auf Baumessen in Chemnitz und Dresden

Auch die jüngsten Hochwasserereignisse zeigen, dass vielerorts das natürliche Rückhaltepotential von Uferbereichen schnell erschöpft ist und angrenzende...

Im Focus: Wie Darmbakterien krank machen

HZI-Forscher entschlüsseln Infektionsmechanismen von Yersinien und Immunantworten des Wirts

Yersinien verursachen schwere Darminfektionen. Um ihre Infektionsmechanismen besser zu verstehen, werden Studien mit dem Modellorganismus Yersinia...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Alle Focus-News des Innovations-reports >>>

Anzeige

Anzeige

IHR
JOB & KARRIERE
SERVICE
im innovations-report
in Kooperation mit academics
Veranstaltungen

Nachhaltige Wassernutzung in der Landwirtschaft Osteuropas und Zentralasiens

19.01.2017 | Veranstaltungen

Künftige Rohstoffexperten aus aller Welt in Freiberg zur Winterschule

18.01.2017 | Veranstaltungen

Bundesweiter Astronomietag am 25. März 2017

17.01.2017 | Veranstaltungen

 
VideoLinks
B2B-VideoLinks
Weitere VideoLinks >>>
Aktuelle Beiträge

Flashmob der Moleküle

19.01.2017 | Physik Astronomie

Tollwutviren zeigen Verschaltungen im gläsernen Gehirn

19.01.2017 | Medizin Gesundheit

Fraunhofer-Institute entwickeln zerstörungsfreie Qualitätsprüfung für Hybridgussbauteile

19.01.2017 | Verfahrenstechnologie