According to a team of scientists at the University of Rochester, a rare mutation in a flu-encoded protein, called Non-Structural protein 1 (NS1), renders the virus defenseless against the body’s immune system. This discovery, reported in the Journal of Virology, could provide a new strategy for a live influenza vaccine.
This pseudo-colored negative-stained transmission electron micrograph depicts the ultrastructural details of an influenza virus particle, or ‘virion.’ Image credit: Cynthia Goldsmith / CDC.
The newly identified mutation weakens the flu virus by making the NS1 protein defunct.
Flu virus needs NS1 to prevent interferon, the immune system’s front line against viruses, from alerting the host cell that it has been infected.
Inhibiting interferon affords the virus time to multiply and spread before the immune system can mount an attack.
“Most people have healthy interferon responses and would quickly and easily fend off this weakened mutant strain of flu, but this virus somehow managed to find the one person that had an interferon defect that allowed it to replicate,” explained study senior author Prof. David Topham.
The probability of this virus surviving and infecting a human is so low – it is as if the team found a needle in a haystack.
The team isolated the mutated virus from a nasal swab of a single flu sufferer who happened to be among the small percentage of people with inadequate interferon responses.
When they looked for the NS1 mutation in a national database, it showed up in just 0.03% of all flu strains reported.
This naturally-occurring ‘attenuating’ flu mutation could provide a new way to make live flu vaccines, which contain viruses that are alive, but attenuated, or weakened, so the vaccine itself does not cause illness in humans.
Prof. Topham and their colleagues suspect their NS1 mutation could be a great way to prevent viruses in the live vaccine from infecting anyone who has normal interferon responses, which is most people.
“There is a need to understand what’s happening with the existing live vaccine and potentially a need to develop a new one,” Prof. Topham said.
“We proposed that the mutation we found could be used to create a live flu vaccine.”
The study also highlights the importance of flu virus surveillance – conducting studies like this one to see how the flu is changing, what flu mutations are circulating in humans and animals, and how those mutations affect virus function.
“Health leaders are not doing enough of that research,” Prof. Topham said.
“The influenza field is largely fixated on studying pandemic or potential pandemic viruses, but those viruses only infect a few dozen people every year whereas seasonal flu infects millions – and yet we don’t study human influenzas closely enough.”
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Marta L. DeDiego et al. An NS1 protein mutation (I64T) affects interferon responses and virulence of circulating H3N2 human influenza A viruses. Journal of Virology, published online August 17, 2016; doi: 10.1128/JVI.01039-16
