A new study has unveiled how influenza A infections work inside the throats and lungs.
Researchers at the MRC-University of Glasgow Centre for Virus Research (CVR) say their findings are important for studying how potential future pandemic flu viruses are created and, potentially, how to improve protection against influenza.
Writing in *PLOS Biology*, the authors found that, in individuals who develop influenza, the airways become a patchwork of ‘tiny’ territories. Viruses within each territory work together to fuel further infection, while each territory fights each other to survive.
Using viruses engineered to produce fluorescent proteins in one of two different colours, the team tracked which viruses could get into cells both in cell cultures and in infected mice.
They found this small defence delay means that, as viruses spread from one cell to the next, they divide their host up into separate microscopic territories.
The study showed how influenza viruses spilling out of a single infected cell can enter the cell’s neighbours together, before any barriers go up, which allows them to help each other out when infecting any further new cells.
Conversely, viruses spreading into that region from elsewhere in the host will only reach the infected cells once barriers have been put in place, and so cannot enter and compete with the viruses that are already there.
Study lead author Anna Sims, from the CVR, said: “This study came from seeing something unexpected down the microscope and looking to find out more. We had previously been using fluorescent viruses in a very standard experiment, but when we looked, we could also see signs that they were fighting.
“The idea that viruses can establish territories in their hosts is incredible to see because, in biology, we observe the establishment and defence of territories in many areas, from ants, to trees, to cancer. We now believe that viruses are doing exactly the same thing in humans, but at a microscopic level.”
Senior study author Dr Ed Hutchinson, also from the CVR, added: “The virus patchwork Anna identified arises from a simple property of the timing of virus replication. This means that it probably applies to many different viruses that spread within their hosts.
“In the case of influenza, we know that new pandemic strains of influenza appear when different influenza viruses get into a host separately, replicate, and then come together to make a new virus as they spread within their host’s airway.
“The work done in this study shows that it is a lot harder than we had thought for influenza viruses to pull this off. This knowledge can now be used to find out what factors help pandemic viruses to overcome these barriers.”
Superinfection exclusion creates spatially distinct influenza virus populations. *PLOS Biology* 9 February 2023.
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