Cytomegalovirus And Tumors

Pathogens & People: Tumors and viruses: What's the connection? By EDWARD McSWEEGAN, For The Capital Published 03/01/09 Whatever your political persuasion, I think you would have to agree that Sen. Ted Kennedy is a lucky man. He has survived decades of ruthless national politics, endless family tragedies, personal legal problems, and, most recently, a deadly form of brain cancer. He's a survivor in every sense What he survived last year was an aggressive brain tumor called glioblastoma multiforme. Each year, 10,000 Americans are diagnosed with it, and it is usually fatal. The ultimate consequences of this brain cancer are no mystery, but the ultimate cause of this deadly illness still is. Some researchers think the cause of Kennedy's type of brain cancer is a virus that is present in 80 percent of the U.S. population. That virus is called Cytomegalovirus. It is a herpes virus in the same family as chickenpox, genital herpes and mononucleosis viruses. CMV is spread by close person-to-person contact, blood transfusions and pregnancy. Studies suggest that between 3 and 11 percent of healthy adults and 50 percent of children shed the virus in urine or saliva. Usually CMV produces a "silent" or symptom-free infection. Yet the virus will persist forever in the host as a "latent" or dormant infection. Does CMV really cause cancers? If CMV permanently infects 80 percent of the U.S. population, why don't most of us have brain tumors? If CMV is contagious, are some brain cancers also contagious? Good questions, but of course, there are no good answers yet. In 2002, a group of scientists found active CMV in the brain tumor tissue of two dozen patients suffering from glioblastoma multiforme. More recently, CMV was found to be active in about 90 percent of such brain tumors. But it's a chicken or egg situation: which came first, the virus to start the tumor or the tumor to awaken the dormant virus? Then there are the statistics. Most Americans have CMV, yet only one in 30,000 gets a glioblastoma. Last summer, Duke University neurologist Duane Mitchell told Scientific American, "Most evidence to date does not support CMV being a cancer-causing virus." The hunt for such viruses began 100 years ago when a Long Island farmer brought a tumorriddled chicken to the Rockefeller Institute in New York City. A curious researcher named Peyton Rous extracted some cancer cells from the bird, ground them up, filtered the resulting solution

and injected it into healthy birds. They all developed tumors from what would later be known as the Rous Sarcoma Virus. Since then, human cervical cancer, liver cancer and a lymphoma have been found to be caused by three different viruses: the Human Papilloma Virus, Hepatitis B Virus and Epstein-Barr Virus. New anti-virus vaccines now can prevent many cases of cervical and liver cancer. Perhaps surprisingly, a CMV vaccine is being tested even though it is not yet clear that CMV causes malignant brain tumors. Because CMV is often "associated" with tumors, the thinking is that an anti-CMV vaccine might be a useful "therapeutic" vaccine (as opposed to a preventive vaccine), and thereby augment the standard radiation, drug and surgical treatments. (It's not clear whether Kennedy received such an experimental vaccine.) The pharmaceutical company Novartis also is working on a CMV vaccine, but this one is intended to prevent CMV infections from starting. Preventing CMV infections may not reduce the number of people who eventually develop brain tumors, but it might help prevent pregnant women from passing the virus to their babies and causing serious birth defects. According the Centers for Disease Control, one in 750 babies the U.S. each year are born with or develop disabilities from a CMV infection. Some of these disabilities include loss of hearing or vision, mental disability, motor problems and seizures. Some symptoms of CMV may not appear for months or even years after birth. These congenital CMV infections typically occur when a woman is infected for the fist time during her pregnancy. These are called primary CMV infections, and they occur in 1 to 4 percent of pregnant women and lead to fetal infections in one-third of pregnancies. In women already carrying latent CMV, the virus then may reactivate, but cause fetal infections in less than 1 percent of pregnancies. CMV is a tricky virus, causing few overt symptoms in healthy adults, but then lying in wait for years or decades, possibly to cause a brain tumor, and certainly to cause serious neonatal infections. There are few reliable measures to prevent CMV infection, and no good anti-viral drugs to treat it. The availability of a preventive CMV vaccine would likely ease the angst of pregnancy and the overall burden of serious disabilities among children.