They have developed a new method to generate virus particles containing labeled viral DNA genomes. This allowed them to visualize, for the first time, single viral genomes in the cytoplasm and the nucleus by using fluorescence microscopy in regular or superresolution mode. The new findings enhance our understanding of how viral disease occurs, and how cells respond to infections.
The medical, humanitarian and economical impact of viral diseases is devastating to humans and livestock. There are no adequate therapies available against most viral diseases, largely because the mechanisms by which viruses infect cells are poorly known. An interdisciplinary team of researchers from the University of Zurich headed by cell biologist Prof. Urs Greber now presents a method that can be used to display viral DNA in host cells at single-molecule resolution. The method gives unexpected insights into the distribution of viral DNA in cells, and the reaction of cells to viral DNA.
Click chemistry detects viral DNA
For their studies, Greber and his team with PhD students I-Hsuan Wang, Vardan Andriasyan and senior research scientist Dr. Maarit Suomalainen used cell cultures and human adenoviruses causing respiratory disease and conjunctivitis, herpes viruses and vaccinia virus, the latter in collaboration with Dr. Jason Mercer and his PhD student Samuel Kilcher from the ETH Zurich. To label the DNA of an intact virus, the scientists turned to click chemistry – widely applicable chemical reaction types. Prof. Nathan Luedtke from the Institute of Organic Chemistry at the University of Zurich, and PhD student Anne Neef developed a new class of “clickable” chemical molecules. “Our molecule is incorporated into viral DNA without affecting the biological functions of the DNA, and it can be used to label the DNA for fluorescence microscopy,” says Luedtke.
Defense response of infected cells visible for the first time
Greber and his team infected human cells in culture with the chemically labeled viruses, and observed the behavior of the viral DNA during entry into cells. “Using this elegant method, we can reveal that not all the incoming viral DNA enters the cell nucleus as originally expected, but a significant fraction remains in the cytosol, the fluids of the cytoplasm,” explains Greber. According to the scientists, this phenomenon may be part of the antiviral defense reaction. “For the first time, we can display the localization of incoming viral DNA, and link it to anti-viral defense or infection mechanisms,” says Greber. The researchers show that cells of the same type take up different amounts of viral DNA into their nucleus. Greber suspects that the nucleus has antiviral defense reactions, akin to the cytosol, and these defense reactions are variable between cells. With the new method in hand, this is now subject to future studies. The scientists suggest that their procedure can be applied to other DNA viruses, or the HI virus (HIV).
I-Hsuan Wang, Maarit Suomalainen, Vardan Andriasyan, Samuel Kilcher, Jason Mercer, Anne Neef, Nathan W. Luedtke & Urs F. Greber. Tracking viral genomes in host cells at single molecule resolution. Cell Host Microbe, October 16, 2013. http://dx.doi.org/10.1016/j.chom.2013.09.004
Prof. Dr. Urs Greber
Institute of Molecular Life Sciences
University of Zurich
Tel. +41 44 635 48 41
Nathalie Huber | Source: Universität Zürich
Further information: www.mediadesk.uzh.ch
Further Reports about: anti-viral defense > biological function > cell death > chemical molecules > DNA > DNA viruses > fluorescence microscopy > human cell > infection mechanisms > single-molecule resolution > viral disease > viral DNA > viral DNA genomes > viral genome
More articles from Life Sciences:
ASU researchers discover chameleons use colorful language to communicate
12.12.2013 | Arizona State University
Sleep-deprived mice show connections among lack of shut-eye, diabetes, age
12.12.2013 | University of Pennsylvania School of Medicine
A unique solar panel design made with a new ceramic material points the way to potentially providing sustainable power cheaper, more efficiently, and requiring less manufacturing time.
It also reaches a four-decade-old goal of discovering a bulk photovoltaic material that can harness energy from visible and infrared light, not just ultraviolet light.
Scaling up this new design from its tablet-size prototype to a full-size solar panel would be a large step toward making solar power affordable compared with ...
Atlantische Flohkrebse pflanzen sich jetzt auch in arktischen Gewässern fort
Biologen des Alfred-Wegener-Institutes, Helmholtz-Zentrum für Polar- und Meeresforschung (AWI), haben zum ersten Mal nachgewiesen, dass sich in den arktischen Gewässern westlich Spitzbergens auch Flohkrebse aus dem wärmeren Atlantik fortpflanzen.
Diese überraschende Entdeckung deute auf einen möglichen Wandel der arktischen Zooplankton-Gemeinschaft hin, berichten die Wissenschaftler und Wissenschaftlerinnen in der Fachzeitschrift Marine Ecology ...
The molecular architecture of three key proteins and their complexes reveals how plants fine-tune their immune response to pathogens
Plants rarely get sick in their natural environment. When the threat of infection arises, a quick decision is made about the necessary countermeasures. The course is set by a protein which forms complexes with its partner proteins for this purpose.
Jane Parker from the Max Planck Institute for Plant Breeding ...
Researchers studying speciation of butterfly orchids on the Azores have been startled to discover that the answer to a long-debated question "Do the islands support one species or two species?" is actually "three species".
Hochstetter's Butterfly-orchid, newly recognized following application of a battery of scientific techniques and reveling in a complex taxonomic history worthy of Sherlock Holmes, is arguably Europe's rarest orchid species. Under threat in its mountain-top retreat, the orchid urgently requires conservation recognition.
A lavishly illustrated publication, titled "Systematic revision of Platanthera in ...
Researchers from Brown University and the University of Hawaii have found some mineralogical surprises in the Moon's largest impact crater.
Data from the Moon Mineralogy Mapper that flew aboard India's Chandrayaan-1 lunar orbiter shows a diverse mineralogy in the subsurface of the giant South Pole Aitken basin.
The differing mineral signatures could be reflective of the minerals dredged up at the time of the giant impact 4 billion years ago, ...
12.12.2013 | Life Sciences
12.12.2013 | Earth Sciences
12.12.2013 | Studies and Analyses
11.12.2013 | Event News
10.12.2013 | Event News
05.12.2013 | Event News