Published today in Communications Biology, La Trobe University researchers found the virus can kill white blood cells – monocytes – through programmed cell death (apoptosis) and induce their fragmentation.
La Trobe Institute for Molecular Science researchers used a series of biochemical approaches and high-resolution microscopy to capture the virus hiding within and on these dying cells fragments.
Lead researcher Dr Georgia Atkin-Smith said this “Trojan Horse” phenomenon may allow the virus to efficiently spread within the body.
“Monocytes are important for our immune system’s ability to destroy invaders and facilitate repair. We can describe this type of white blood cell as something akin to reserve forces in the military,” Dr Atkin-Smith said.
“We discovered the virus can effectively infiltrate these vital cells, triggering their death and fragmentation through a process we call the ‘dance of death’. These tiny fragments can then act as Trojan Horse vesicles, harbouring a series of viral components that can both aid viral spread and induce an important anti-viral immune response.”
The researchers also discovered that a commonly prescribed anti-psychotic could limit the spread of the Influenza A virus in laboratory cell culture assays and preliminary mouse models.
“We discovered Haloperidol can inhibit the fragmentation of dying cells in our early drug trials. By blocking dying cell fragmentation, the drug could limit the spread of the virus through this novel pathway” Dr Atkin-Smith said.
Influenza A virus was linked to more than 700 deaths in Australia in 2019. Globally, the virus causes three to five million cases of severe illness each year and is responsible for an estimated 290,000 to 690,000 respiratory deaths annually.
Dr Atkin-Smith said finding novel ways viruses can spread is essential for the development of new therapeutics.
“Influenza viruses can frequently mutate. While flu vaccines are incredibly important, their effectiveness varies from 40 to 60 per cent in Australia,” Dr Atkin-Smith said.
“Where a flu vaccine works to build your immune system to fight against infection, we’re working to discover a way to overcome the virus once infection has occurred.”
This discovery builds on earlier research from La Trobe cell biologist Associate Professor Ivan Poon, who first discovered the final stages of cell death and the ways in which dying cells are removed from the body.
“For more than 50 years, scientists thought cell fragmentation was a random process and dying cell fragments were just debris in the body,” Associate Professor Poon said.
“This study is the first to demonstrate dying cell fragments can aid the trafficking of influenza A virus between dying and healthy cells. The continuation of this research is important for the development of new therapeutics for infectious diseases.”
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