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In the tubular system of human cells

Scientists from the Hygiene Institute at the Heidelberg University Hospital have succeeded for the first time ever in showing the three-dimensional architecture of the dengue virus replication and assembly sites in human cells. Their paper was recently published in the renowned journal “Cell Host & Microbes”.

Dengue fever is the most common infectious disease transmitted by mosquitoes; 100 million people around the world suffer from dengue fever. Scientists from the Hygiene Institute at the Heidelberg University Hospital have succeeded for the first time ever in showing the three-dimensional architecture of the dengue virus replication and assembly sites in human cells. Their paper gives insights into the exact process of virus replication and is a model for other viruses whose replication is not yet known, including hepatitis C viruses. In addition, the researchers’ findings also open up new strategies for new dengue fever treatment and prevention strategies. Up until now, there are no vaccinations or specific antiviral therapies available to counteract the infection.

Title picture of the current “Cell Host & Microbes” issue. The grey structure in the background shows a two-dimensional electron microscope image of a dengue virus. The three-dimensional virus model in the foreground shows the tubes of the endoplasmic reticulum and its balloon-like invaginations where the dengue virus replicates its genome. © Hygiene Institute Heidelberg

Professor Dr. Ralf Bartenschlager, Director of the Department of Molecular Virology at the Institute of Hygiene, and his team, in cooperation with colleagues from the European Molecular Biology Laboratory (EMBL), have published their research in the current edition of the renowned journal “Cell Host & Microbes”.

Viruses modify human cell membranes for their purposes

Viruses lack an own metabolism and are unable to produce proteins from viral RNA or DNA alone. Viruses depend on a host cell for replication – but how and where does replication take place? The answer to this question is of decisive importance for the development of therapies.

Dengue viruses replicate in the endoplasmic reticulum, an interconnected network of vesicles and tubules connected to the nuclear envelope, where proteins are synthesised. The dengue viruses use this membrane system and modify it for their replication.

“We now know that viral RNA is replicated in the tubules of the endoplasmic reticulum and is moved across the membrane of the endoplasmic reticulum (ER) through tiny pores. We were also able to show that the replication of the viral genome and its encapsulation into new viruses are directly coupled with each other,” said Professor Bartenschlager. The new viral genomes are transported through tiny pores across the ER into the intracellular space where they are incorporated into viral prestages which then enter the ER a second time. During this process, the viruses are equipped with a membrane envelope which gives them the appearance of normal cellular freight and enables them to pass the ER membrane unhindered. The replication cycle can then begin again.

Original publication:
Sonja Welsch, Sven Miller, Ines Romero-Brey, Andreas Merz, Christopher Bleck, Paul Walther, Stephen D. Fuller, Claude Antony, Jacomine Krijnse-Locker, Ralf Bartenschlager, Composition and Three-Dimensional Architecture of the Dengue Virus Replication and Assembly Sites, Cell Host & Microbes 2009, 5, 4.

Contact:
Prof. Dr. Ralf Bartenschlager
Department of Molecular Virology
Medical Faculty
Heidelberg University Hospital
Im Neuenheimer Feld 345
69120 Heidelberg
Tel.: +49 (0)6221 / 56 45 69
E-mail: Ralf_Bartenschlager(at)med.uni-heidelberg.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/in-the-tubular-system-of-human-cells