A team of scientists from the University of Glasgow's Vet School have received a grant of £800,000 from the Wellcome Trust to research a mechanism that blocks a critical step in the replication cycle of retroviruses. In the long term, the research could lead to the design of new therapeutic strategies or drugs against retroviruses, which cause diseases such as certain leukemias and the type of cancer that killed Dolly the sheep, the world's first cloned mammal.
Mammals have evolved several mechanisms to fight viral infections, and insight into how humans and animals successfully limit virus spread helps to develop effective anti-viral drugs and vaccines.
The new research is directed towards understanding the mechanisms of retrovirus-induced cell transformation. The scientists are set to further investigate a chemical that may be able to stop so-called retroviruses in their tracks. Retroviruses, during their life cycle, spread by permanently by inserting their genetic material into healthy cell's DNA.
The scientists, led by Professor Massimo Palamrini from the University of Glasgow's Faculty of Veterinary Medicine, are investigating how some endogenous retroviruses ('benign' retrovirusese present in the genome of all mammals) protect hosts by interfering with the infection by related disease-causing retroviruses.
The University of Glasgow recently recruited Professor Massimo Palmarini, a world-leading expert in viral pathogenesis and lung cancer. Most recently of the University of Georgia, USA, Professor Palmarini now leads a team of top molecular cancer specialists and virologists at Glasgow and is set to continue his groundbreaking work into a virus induced type of lung cancer, the disease which led to the demise of Dolly the sheep, the world's first cloned mammal
His expertise spans the fields of viral pathogenesis, infectious disease and cancer. The major focus of Professor Palmarini's research is the study of a naturally occurring contagious lung cancer of sheep that cannot currently be controlled, and leads to significant economic loss in the UK and beyond. Professor Palmarini has pioneered research on the cancer causing agents in a retrovirus-induced lung cancer of sheep known as ovine pulmonary adenocarcinoma (OPA). Research into the mechanisms underlying this form of lung cancer could provide strategies to understand the onset and progression of human lung cancer, the leading cause of deaths in cancer patients.
The new grant will boost the study of how an 'endogenous' retroviruses (ERV) named enJS56A1 interferes with a pathogenic 'exogenous' retrovirus (JSRV), the cause of major infectious diseases of sheep. enJS56A1 forms viral particles that 'stick' together and cannot exit the cell and spread to other cells. JSRV instead forms particles normally able to exit the cell. However, when JSRV and enJS56A1 are present in the same cell only defective 'sticky particles' are formed, effectively blocking viral infection.
Understanding the mechanisms of enJS56A1-induced block can lay the foundation to develop new drugs that stop production of viruses from infected cells.
The research is set to shed light on how retroviruses evolve and will help explain late steps in the retroviral life cycle. Understanding how enJS56A1 functions could provide a model for designing new anti-retroviral therapies that work on cells already infected by retroviruses. Many current anti-retroviral drugs function only immediately after the virus infects a new cell.
Professor Palamarini, from the University of Glasgow's Veterinary Faculty, said: "The grant is set to develop much needed research into viral infections. We need to understand more about how retroviruses work and there may be subtle differences between different retroviruses. The research could eventually lead to new treatments to fight retroviruses."
"Like all viruses, retroviruses insert their genetic material into host cells and then force the host to make copies of the virus. Unlike other viruses, however, retroviruses permanently insert a copy of their genes into the genome of cells they invade. Every sheep on the planet has retroviruses that are present in the genome like every other gene. In fact, all animal species - humans included - have retroviruses that are genetically inherited."