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DNA Helix

Posts Tagged ‘virus’

Scientists discover DNA knot keeps viral genes tightly corked inside shell

A novel twist of DNA may keep viral genes tightly wound within a capsule, waiting for ejection into a host, a high-resolution analysis of its structure has revealed.

A donut-shaped twist, or toroid, of DNA (shown in red) wedges the viral genome tightly within the protein envelope of the bacteriophage.Using electron microscopy and three-dimensional computer reconstruction, UC San Diego biologists and chemists have produced the most detailed image yet of the protein envelope of an asymmetrical virus and the viral DNA packed within, they report this week in the journal Structure. The image, with a resolution of less than a nanometer, or a millionth of a millimeter, will help to unravel how the virus locks onto its host and infects the cells by injecting its DNA.

By assembling more than 12,000 microscopic views of frozen viral particles from different angles, UCSD chemists Jinghua Tang, Norman Olson and Timothy Baker, a professor of chemistry and biological sciences, have determined the structure of a bacteriophage called phi29 with a resolution finer than 8 Angstroms (one Angstrom equals a tenth of a nanometer). Their project was part of a long-term collaboration with molecular virologist Dwight Anderson and his colleagues at the University of Minnesota.

Although the structures of spherical viruses with a high degree of symmetry have been resolved using similar methods, many more images were required to accomplish the same task for the head-and-tail shape of phi29. The UCSD scientists said their images of phi29 are twice as fine as those created in previous efforts to visualize viruses with a similar shape.

A comparison between images of the virus with and without its DNA cargo revealed that the DNA twists tightly into a donut shape, or toroid, in the neck of the virus between its head and tail. “This highly distorted DNA structure is unlike anything previously seen or even predicted in a virus,” said Timothy Baker who headed the research team. “It’s an improbably tight turn for DNA, which is generally considered inflexible over very small distances.”

During assembly of the virus, a molecular motor in the neck winds the DNA strand into a tight coil within the head. “It’s under tremendous pressure — about 20 times that of champagne in a bottle,” said Tang, the lead author of the paper.

The knot-like shape of the toroid, along with interlocking bumps in the protein envelope, may keep the DNA wedged into the capsid until the virus docks onto the host cell.

“It’s poised in this tube waiting to go through the bacterial wall,” Baker said. “All of the components work together to create an infection machine.”

Source: University of California – San Diego

DNA Poised for Release in Bacteriophage ø29. Jinghua Tang, Norman Olson, Paul J. Jardine, Shelley Grimes, Dwight L. Anderson, and Timothy S. Baker. Structure. June, 2008: 16 (6).

Josh says:

Biology continues to amaze us. It makes sense for the DNA to be tightly packed and under a lot of pressure, thereby ensuring it is effectively delivered to the host upon infection. I’m sure there was a strong selection in favor of the viral particles that did this the best.

Viruses may play a role in lung cancer development

Papers presented at the 1st European Lung Cancer Conference, jointly organized by the European Society for Medical Oncology (ESMO) and the International Association for the Study of Lung Cancer (IASLC) in Geneva, Switzerland highlight emerging evidence that common viruses may contribute to the development of lung cancer.

Experts agree that smoking is by far the most important factor that contributes to lung cancer development. But other factors can play a role in some cases.

In one report at the conference (Abstract No. 124PD; Friday 25th April, 09:50) Dr. Arash Rezazadeh and colleagues from the University of Louisville, Kentucky, USA, describe the results of a study on 23 lung cancer samples from patients in Kentucky.

The researchers found six samples that tested positive for the presence of human papilloma virus (HPV), the virus that also causes many cases of cervical cancer. One was later shown to be a cervical cancer that had spread to the lungs.

Of the remaining 5 virus-positive samples, two were HPV type 16, two were HPV type 11 and one was HPV type 22. “The fact that five out of 22 non-small-cell lung cancer samples were HPV-positive supports the assumption that HPV contributes to the development of non-small-cell lung cancer,” the authors say.

All the patients in this study were also smokers, Dr. Rezazadeh notes. “We think HPV has a role as a co-carcinogen which increases the risk of cancer in a smoking population,” he says.

In another paper (Abstract No. 125PD; Friday 25th April, 09:50), Israeli researchers suggest that measles virus may also be a factor in some lung cancers. Their study included 65 patients with non-small-cell lung cancer, of whom more than half had evidence of measles virus in tissue samples taken from their cancer.

“Measles virus is a ubiquitous human virus that may be involved in the pathogenesis of lung cancer,” says lead author Prof. Samuel Ariad from Soroka Medical Center in Beer Sheva, Israel. “Most likely, it acts in modifying the effect of other carcinogens and not as a causative factor by itself.”

Source: European Society for Medical Oncology

Trojan horse of viruses revealed

The vaccinia virus has a problem: it is a giant among viruses and needs a special strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius and Postdoc Jason Mercer from ETH Zurich’s Institute for Biochemistry have now discovered what this strategy is. In the process, they stumbled upon new and surprising findings.

The invasion strategy

In order to infiltrate a cell, the vaccinia virus exploits the cellular waste disposal mechanism. When a cell dies, other cells in the vicinity ingest the remains, without needing waste disposal experts such as macrophages. The cells recognize the waste via a special molecule, phosphatidylserine, which sits on the inner surface of the double membrane of cells. This special molecule is pushed out as soon as the cell dies and is broken into parts. The vaccinia virus itself also carries this official waste tag on its surface. “The substance accumulates on the shell of vaccinia viruses”, Jason Mercer explained. The pathogen disguises itself as waste material and tricks cells into digesting it, just as they normally would with the remains of dead cells. As the immune response is simultaneously sup-pressed, the virus can be ingested as waste without being noticed. … Continue Reading »

Potential viral therapy weapon for difficult cancers is safe and effective in study

Combining a herpes virus genetically altered to express a drug-enhancing enzyme with a chemotherapy drug effectively and safely reduced the size of highly malignant human sarcoma grafted into mice. This new finding may add to the growing arsenal of so called oncolytic viruses under development as novel cancer treatments, especially for difficult, inoperable tumors, according to a research led by Cincinnati Children’s Hospital Medical Center and published April 24 in Molecular Therapy.

“Our study shows the chemotherapy drug cyclophosphamide (CPA) enhances the anti-tumor effectiveness of the oncolytic virus rRp450 in mice carrying aggressive human sarcoma, resulting in significant tumor shrinkage,” said Timothy P. Cripe, M.D., Ph.D., a physician and researcher at Cincinnati Children’s and the study’s corresponding author. “Just as important is the fact that the combination of rRp450 and CPA appears to be well tolerated, because non-cancer bearing mice treated with the therapy survive long term. It will take some time to continue developing this approach before its potential to be tested in clinical trials, but our results are encouraging and warrant further study.” … Continue Reading »

Cedars-Sinai Medical Center opens patient trial of virus that attacks brain cancer cells

A common, naturally occurring virus that attacks cancer cells but appears to be harmless to normal cells is being studied as a possible treatment for malignant, highly aggressive and deadly brain tumors called gliomas. Researchers at Cedars-Sinai Medical Center are among a few in the United States evaluating this experimental therapy.

Over the course of a lifetime, most adults will be exposed to the virus in its natural state. It commonly infects the lungs and intestines but – unlike most viruses – causes few if any symptoms and is usually eliminated by the body within two weeks. But while the reovirus (respiratory enteric orphan virus) may be harmless to normal cells, it can specifically kill certain cancer cells. … Continue Reading »

‘Alien’-type viruses to treat MRSA

New methods that involve sticking thousands of bacteria-killing viruses to wound dressings are offering ways to prevent hospital operating theatres from spreading infections, scientists heard today (Tuesday 1 April 2008) at the Society for General Microbiology’s 162nd meeting being held this week at the Edinburgh International Conference Centre.

Although they are too small to see with the naked eye, bacteria are also attacked by viruses, but specific ones that only infect bacteria, not human or animal cells. But for bacteria they present a threat like the alien life form in the Hollywood film Alien – growing inside the bacteria and then bursting out to attack other similar bacteria, continuing their life cycle. Now doctors are harnessing these little alien creatures to help prevent the spread of hospital superbugs by developing materials impregnated with thousands of tiny beads coated in bacteria-killing viruses. … Continue Reading »

Chips could speed up detection of livestock viruses

Some of the worst threats to farm workers and farm animals such as bird flu, foot-and-mouth disease and other emerging viruses could soon be quickly identified by using a simple screening chip developed by scientists from the Institute for Animal Health, scientists will hear today (Monday 31 March 2008) at the Society for General Microbiology’s 162nd meeting being held this week at the Edinburgh International Conference Centre.

“The last major SARS outbreak – severe acute respiratory syndrome – which started on the border of China and Hong Kong was identified using a microarray chip. Fortunately, because of the rapid identification of the virus it was brought under control, and in spite of its seriousness caused relatively few deaths,” says Dr Paul Britton of the Institute for Animal Health in Compton, near Newbury, Berkshire. “We need a similar way of quickly identifying viruses that attack chickens, cattle, pigs, sheep and other farm animals.” … Continue Reading »

Virus selectively kills tumor cells in the brain

Researchers at the University of Alabama at Birmingham have successfully tested a virus which targets only brain cancer cells in mice. The researchers implanted cancer cells into mice brains and then injected the mice with the virus. While the virus’s progress in the mice was tracked in real-time using florescent “markers,” the virus attacked and destroyed the brain tumors without affecting non-tumorous tissue. The original paper can be found in The Journal of Neuroscience.

I’ve read several papers recently where a virus has been used to selectively target and destroy tumor cells. I don’t know of a general surface protein or receptor that is common to all tumors; if there indeed isn’t one, then these viruses will have to be engineered to be specific for a particular type of cancer rather than having just one virus that would eradicate all cancer. It’s going to be an exciting next couple years in cancer research and treatment.