Bird flu virus that infected a person in Missouri had a rare mutation

Genetic analysis of a bird flu virus detected in a person in Missouri who didn’t previously have contact with animals offers more details on the case, but experts say there isn’t substantial evidence to suggest human-to-human transmission is happening.

A bird flu virus that infected a person in Missouri who didn’t have any known animal exposures had two mutations not seen in previous human cases. So far, there is little reason to believe these changes have improved the virus’s ability to spread among people.

A transmission electron micrograph of an H5N1 virus
Phanie – Sipa Press / Alamy Stock Photo


Since March, the bird flu virus known as H5N1 has been circulating amongst dairy cows in 14 US states. The virus, which has killed millions of birds and thousands of mammals worldwide, isn’t believed to transmit between people. However, each time it infects a person, it has the ability to develop mutations that may change this.


On 6 September, the Missouri Department of Health & Senior Services announced a person in the state had tested positive for the virus. This is the 14th person in the US known to have contracted the virus and the first to report no exposure to animals. All previous cases occurred in people who had close contact with infected dairy cattle or farmed birds. The person wasn’t exposed to raw milk, which can contain high amounts of the virus. Plus, H5N1 hasn’t been detected in Missouri dairy herds. This has left public health experts unclear as to how this person contracted the virus.


The individual tested positive after being hospitalised for other underlying health conditions and experiencied nausea, vomiting, diarrhoea and weakness. They were not severely ill and have fully recovered, according to the US Centers for Disease Control and Prevention (CDC).


Just as worryingly, another person in their household fell ill with similar symptoms on the same day. However, they weren’t tested for influenza and have since recovered.


Due to low amounts of genetic material in the sample, the CDC has only been able to partially sequence the virus’s genome. The analysis revealed two mutations not seen in previous human cases, both of which occurred in a protein called hemagglutinin. This protein is similar to the spike protein of SARS-CoV-2 in that it helps the virus bind to and infect cells.


One of the mutations, called A156T, has been identified in fewer than 1 per cent of samples collected from dairy cows. Previous research by Jesse Bloom at the Fred Hutchinson Cancer Center in Washington state and his colleagues suggested this mutation can diminish the ability of antibodies to recognise and neutralise the virus.


This is relevant when it comes to vaccine development. Both the CDC and the World Health Organization have been creating weakened versions of H5N1 that can be used to manufacture vaccines if a wider outbreak ever occurs in humans. Bloom and his team have shown A156t causes a 10-to-100-fold drop in the neutralisation ability of antibodies from ferrets treated with vaccine candidates. This means vaccines made with strains that have this mutation won’t be viable – only one potential vaccine strain has remained effective.


“This mutation is not changing our assessment of the risk that this virus will take off in humans, per se,” says Bloom. “It is just showing that we need to think carefully about which vaccine candidates we want to have ready in case that should happen.”

Very little is known about the second mutation, which has only been seen in one dairy cow sample. Early analysis from Bloom and his team indicate it may modestly improve the virus’s ability to bind to influenza receptors that are more prevalent in humans than birds. However, substantially more evidence is needed before experts suggest the virus has an increased capacity to infect people, says Bloom.


This is especially true given the CDC wasn’t able to fully sequence the virus, says Seema Lakdawala at Emory University in Georgia. Mutations elsewhere in the genome could also impact the virus’s ability to bind to human receptors. “There is no indication, at this point, that there is an increased risk of human-to-human transmission,” says Bloom.


Even though we have very little certainty about the details of the latest human infection, the fact someone contracted H5N1 without a known animal exposure is concerning. It suggests our current surveillance system – which mostly monitors those exposed to sick animals – may allow some cases to go undetected, says Meghan Davis at Johns Hopkins University in Maryland.

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