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New research offers hope for Kaposi’s sarcoma

New research published by Worldwide Cancer Research scientist Professor Adrian Whitehouse and his team points to a potential new way to prevent the rare cancer Kaposi’s sarcoma. Their work is published in the journal Nature Microbiology this week.

Kaposi’s sarcoma appears as localised tumours which affect the skin and internal organs. It develops in some people, especially those with weakened immune systems, following infection with a virus called KSHV. Kaposi’s is controllable through palliative treatment, but it remains incurable, and there is currently no form of antiviral treatment or vaccine to fight KSHV.

Now Professor Whitehouse and colleagues at the University of Leeds think they have found a new way to tackle KSHV and other similar viruses. The researchers found that the viruses hijack a group of human proteins, called TREX, and use them to replicate inside our cells. Using this knowledge, they were then able to identify a new compound which blocks the interaction of the virus and TREX proteins.

The researchers will now focus on taking the potential new treatment from the lab bench to clinical studies in humans.

“We still have a lot of work to do,” said Dr Richard Foster, who’s group collaborated on the work, “but bringing together a target point and a compound is a significant finding. Now our job is to improve the quality and potency of the compound before it can operate as a future antiviral drug.”

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“The funding of a postdoctoral research scientist allowed the identification of an essential virus-host interaction, which we have since gone on to target using small molecule inhibitors. Preventing this virus-host cell interaction stops the human tumour virus, Kaposi’s sarcoma-associated herpesvirus, replicating and causing disease”.

As well as blocking KSHV the researchers also found the compound could be active against a number of related viruses, meaning the potentially new antiviral might be effective not just against KSHV, but could also be used to treat a range of herpesvirus-associated conditions, from cold sores to congenital infections in newborn babies.

“Professor Whitehouse and his team have discovered a potential way of preventing the rare, but devastating, Kaposi’s sarcoma from developing.” Explains Dr Lynn Turner, Head of Research at Worldwide Cancer Research. “Their findings not only offer hope for those who are at risk of developing this disease but also to millions of others infected by similar viruses. It’s exactly this kind of discovery research that needs to be supported in order to pave the way for advances in cancer research and biomedical research in general.”

Some text for this article was adapted from a University of Leeds press release, read the full article here.

The full scientific article reference is: Sophie Schumann, Brian R. Jackson, Ian Yule, Steven K. Whitehead, Charlotte Revill, Richard Foster, Adrian Whitehouse. Targeting the ATP-dependent formation of herpesvirus ribonucleoprotein particle assembly as an antiviral approach. Nature Microbiology, 2016; 2: 16201 DOI: 10.1038/nmicrobiol.2016.201. Find the scientific paper online here.

This research was supported by Worldwide Cancer Research, Wellcome Trust, and Biotechnology and Biosciences Research Council.

Image courtesy of University of Leeds. 

Further information

We have funded Professor Whitehouse’s work on Kaposi’s since 2012. Read about his work with us here and here.

Search our other Kaposi’s sarcoma projects here.

Stopping Kaposi’s Sarcoma-associated herpes virus (KSHV) in its tracks

Professor Adrian Whitehouse is finding new ways to stop the virus which causes Kaposi’s sarcoma- a rare form of cancer affecting the skin and internal organs.

The virus, known as KSHV, can cause Kaposi’s sarcoma in people with weakened immune systems. People who have AIDS or have had an organ transplant for example can be especially vulnerable.

“We currently don’t have any form of antiviral or vaccine to fight KSHV,” says Professor Whitehouse. “Meanwhile Kaposi’s sarcoma is becoming more and more common in some parts of the world. For example, because of the AIDS epidemic, Kaposi’s sarcoma is now the most common reported adult tumour in sub-Saharan Africa.”

Professor Whitehouse and his team have been studying exactly how KSHV manipulates the human cells it infects to improve its own survival. “Finding a way to block replication of the virus inside infected cells could be a way to stop Kaposi’s sarcoma developing,” says Professor Whitehouse. “We have exciting early data which suggests that KSHV uses a specialised gene expression mechanism in the cell to replicate its own genetic material. We now need to investigate exactly how and why the virus uses this mechanism- that’s our aim for this project.”

“Ultimately we want to find out whether blocking this cell mechanism could potentially be a new antiviral treatment strategy for Kaposi’s sarcoma and other KSHV-associated diseases.”

How do T cells control Kaposi’s sarcoma associated herpes virus infection in cells?

Several viruses are known to cause cancers. One such virus is Kaposi's sarcoma-associated herpes virus (KSHV). KSHV is the cause of Kaposi's sarcoma (KS), which is a type of cancer that is often associated with skin lesions, as well as two other cancerous diseases. KS is often associated with AIDS, and with the high prevalence of AIDS in Africa, it is now one of the most commonly reported adult tumours in sub-Saharan Africa. Research so far has found that T cells, a type of immune cell, are most likely involved in controlling infection and damage caused by the virus. When KSHV causes KS, and other diseases, the virus produces a group of proteins, and these proteins are how the T cells detect the virus as a foreign body. Dr Hislop and his team have identified specific T cells, which recognise these virus proteins, and they have been able to isolate these T cells to study how they attack KHSV. Some of these virus proteins use methods that may prevent them from being recognised by the T cells. They will now test how T cells interact with these proteins to, firstly, better understand how the proteins prevent being detected by T cells, and secondly they will explore ways of restoring T cell recognition of these proteins. Thirdly they will study whether different types of T cells are better at recognising cells infected with the virus. In earlier research, they found that the T cells were able to recognise some types of cells that were infected with KHSV, but that the T cells were unable to kill these cells. Based on these findings, they will now study whether a virus protein is involved in stopping the T cells from killing KSHV-infected cells, and how they can prevent this from happening.

Investigating new treatments against Kaposi’s Sarcoma-associated herpesvirus

Several viruses are known to cause cancers. One such virus is Kaposi’s sarcoma-associated herpesvirus (KSHV). KSHV is the cause of Kaposi’s sarcoma (KS), which is a type of cancer that is often associated with skin lesions, as well as two other diseases. KS is often associated with AIDS, and with the prevalence of AIDS in Africa being so high, it is now the most commonly reported adult tumour in sub-Saharan Africa. There are currently no vaccines or antiviral treatments against KSHV. The virus multiplies and spreads throughout the body by bursting the human cells (called lytic replication) in which they are living. This mechanism plays a big role in causing disease and tumour growth. Researchers therefore want to aim new treatments at stopping lytic replication. Professor Whitehouse will be using his Worldwide Cancer Research grant to study proteins that are involved in the spread of the virus, with the aim to find a way of blocking virus spread, and thereby stopping development of KS.