Study findings could open new possibilities for treating cancer with adenovirus

Adenovirus is a common virus that causes infectious diseases of the respiratory tract, eyes and gastrointestinal tract in humans and animals. Researchers at Umeå University study molecular mechanisms of infection in order to understand how adenovirus causes disease.

The researchers in Umeå, together with research groups from Germany, the UK and Hungary, have now discovered a new type of mechanism used by a rare adenovirus type to attack cells.

Human Adenovirus type 52 (HAdV-52) is one of the few adenoviruses that has two different types of fiber proteins on its surface, which are 'used' by the virus for the attachment to target cells. In collaboration with researchers in the Glycosciences Laboratory at Imperial College in London, who are world leading in the research field of glycobiology, the scientists have shown that the shorter fiber binds to an unusual type of carbohydrate-based receptor, polysialic acid (a long chain of repeated sialic acids). Annasara Lenman working with Niklas Arnberg has subsequently corroborated that HAdV-52 binds to polysialic acid on target cells, and that this leads to infection. In collaboration with experts in structural biology at the University of Tübingen, the interaction between the short fiber and polysialic acid has been mapped at the atomic level.

"We knew earlier that the short fiber binds to sialic acid, but not how the underlying carbohydrate chain was constructed," explains Annasara Lenman postdoc at the Department of Clinical Microbiology and The Laboratory for Molecular Infection Medicine Sweden (MIMS) at Umeå University, Sweden.

As polysialic acid is overexpressed on cancer cells in the brain and lungs, our findings could open new possibilities to use HAdV-52 for treatment for the corresponding types of cancer.

For a long time, adenovirus and other viruses have been considered suitable weapons for the treatment of different types of cancer. Viruses can kill cancer cells themselves, but in recent years it has also been understood that a virus infection in a tumor can activate the immune system against the cancer cells. You can also "arm" viruses with different genes that can for example counteract the development of resistance against different drugs. A major challenge has been to target viruses specifically against the cancer cells.

"Most adenoviruses tested so far have only one type of cell-binding fiber. HAdV-52 has two different fibers, one of which has a natural predilection for cancerous cells that express polysialic acid. This opens up a more effective harnessing of viruses against the right kind of cells", Annasara Lenman explains.

The results can also be of importance in other research areas:

"Perhaps the most important function of polysialic acid is its contribution to the brain's development. However, one has not known much about how polysialic acid interacts with its environment. Our research makes it pertinent to investigate whether polysialic acid plays a part in brain development by interacting with specific cellular molecules." says Annasara Lenman.

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