Influenza and the Trojan Horse effect

A Melbourne research team, led by La Trobe University, has revealed that influenza A virus can kill key white blood cells and hide among them like a Trojan Horse to aid its spread in the body. Their work has been published in the journal Communications Biology.

Influenza A 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; more than 700 of these deaths occurred in Australia in 2019. Now, researchers have found that the virus can kill white blood cells known as monocytes through programmed cell death (apoptosis) and induce their fragmentation.

The researchers used a series of biochemical approaches and high-resolution microscopy to capture the virus hiding within and on these dying cells fragments. According to La Trobe’s Dr Georgia Atkin-Smith, lead researcher on the study, 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,” Dr Atkin-Smith said. “We can describe this type of white blood cell as something akin to reserve forces in the military.

“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 found that a commonly prescribed antipsychotic could limit the spread of influenza A virus in laboratory cell culture assays and preliminary mouse models, with Dr Atkin-Smith saying, “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 finding novel ways viruses can spread is essential for the development of new therapeutics, noting, “Influenza viruses can frequently mutate. While flu vaccines are incredibly important, their effectiveness varies from 40 to 60% in Australia.

“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.”

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