Image: Human airway epithelial cells infected with measles virus. The green cells are infected with a measles virus that is engineered to glow green. The red cells are uninfected.
A new study by researchers at Mayo Clinic and the University of Iowa has identified a receptor protein that allows measles virus to enter the airway cells — the virus’s point of departure from the host.
“We have identified a cell-specific receptor that is not involved in the initial infection, but is involved in the final stages of the viral life cycle before the virus gets released when it’s coughed out,” says Patrick Sinn, Ph.D., assistant professor of pediatrics at the UI Roy J. and Lucille A. Carver College of Medicine.
The findings, which are published Nov. 2 in the Advance Online Publication of the journal Nature, also show that the receptor, known as nectin-4, is required for measles virus to spread from cell to cell within the airway’s epithelial layer. This spread creates large patches of infected cells poised to release virus into the airways where it can be expelled.
Measles virus affects more than 10 million children worldwide each year and accounts for approximately 120,000 deaths. In the United States, vaccination and good health care mean that deaths from measles are rare. However, the disease can still cause serious complications for young children, such as pneumonia and deafness, and miscarriage in pregnant women. In recent years, the spread of the virus has increased due to lack of sufficient vaccine coverage and prevalence of international travel — meaning it’s still a significant public health problem in the United States.
Using measles virus to fight cancer
In addition to improving understanding of measles virus and how it spreads, the new study findings also have implications for cancer therapy.
Previous work has shown that measles virus infects and destroys certain cancer cells. Modified measles virus is currently being tested at Mayo Clinic as an anti-cancer therapy for ovarian cancer, glioblastoma multiforme (a type of brain cancer), and multiple myeloma.
Nectin-4, the newly discovered measles receptor, is normally expressed only on epithelial cells in the airway. However, certain cancer types, including ovarian, breast and lung cancers, also express the receptor on their cell surfaces. The new findings suggest that the presence of nectin-4 on cancer cells may mean they can be targeted with measles virus, which researchers hope will prove to be a less toxic treatment than chemotherapy or radiation.
In addition to Sinn, UI researchers Paul McCray, M.D., professor of pediatrics, and genetics graduate student Shyam Ramachandran also were involved in the study. The team also included scientists from the Paul Ehrlich Institute in Germany, the Armand Frappier Institute in Montreal, Canada, the University of Aix-Marseille in France and the National University of Singapore/Duke University.
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