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The influenza virus turns infected lung cells into factories that churn out thousands of copies of the virus to spread the infection. St. Jude Children's Research Hospital scientists have reported a promising new approach that uses an investigational cancer drug to dial down viral production and dramatically increase survival of flu-infected mice. The findings appear in the journal Cell Reports.
"Previously, little was known about how flu infection changed the metabolism of lung epithelial cells; but based on early evidence in this study we suspected metabolism was an Achilles heel of the virus," said corresponding author Paul Thomas, Ph.D., an associate member of the St. Jude Department of Immunology. "We were not disappointed."
Researchers showed that flu infection changed the metabolism of human lung epithelial cells, the prime location for replication of flu virus. The alteration radically increased the cells' dependence on glucose and glutamine, which are the raw materials of viral production. PET scans showed dramatically increased glucose metabolism in the lungs of 20 immune-compromised pediatric cancer patients with flu and other respiratory infections compared to patients without infections.
Working with colleagues who study rapidly dividing tumor cells, the researchers screened 80 small molecules and drugs that targeted cell metabolism rather than the virus. The scientists identified several, including the investigational cancer drug BEZ235, which blocked a key metabolic pathway in flu-infected human lung epithelial cells.
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"Previously, little was known about how flu infection changed the metabolism of lung epithelial cells; but based on early evidence in this study we suspected metabolism was an Achilles heel of the virus," said corresponding author Paul Thomas, Ph.D., an associate member of the St. Jude Department of Immunology. "We were not disappointed."
Researchers showed that flu infection changed the metabolism of human lung epithelial cells, the prime location for replication of flu virus. The alteration radically increased the cells' dependence on glucose and glutamine, which are the raw materials of viral production. PET scans showed dramatically increased glucose metabolism in the lungs of 20 immune-compromised pediatric cancer patients with flu and other respiratory infections compared to patients without infections.
Working with colleagues who study rapidly dividing tumor cells, the researchers screened 80 small molecules and drugs that targeted cell metabolism rather than the virus. The scientists identified several, including the investigational cancer drug BEZ235, which blocked a key metabolic pathway in flu-infected human lung epithelial cells.
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