Many H3N2 virus strains which are circulating in pigs and birds are genetically very similar to the 1968 “Hong Kong” flu, also an H3N2 strain that spread around the world and eventually killed approximately one million people, a new study carried out at MIT (Massachusetts Institute of Technology) has found.

The researchers added that current flu vaccines may not be effective against these H3N2 strains that currently circulate only in animals. Their study has been published in the journal Scientific Reports (May 10th, 2013 issue).

Study leader, Ram Sasisekharan, said:

“There are indeed examples of H3N2 that we need to be concerned about,” says Sasisekharan, who is also a member of MIT’s Koch Institute for Integrative Cancer Research. “From a pandemic-preparedness point of view, we should potentially start including some of these H3 strains as part of influenza vaccines.”

Over the last century, notable flu pandemics have often emerged from birds and pigs. When a swine or avian flu virus acquires the ability to infect human beings, it often invades by bypassing the immune system, which is only able to detect strains that commonly infect humans.

The good news is that since the 1968 Hong Kong flu pandemic, many H3N2 strains have been circulating in humans. They have become less deadly, and are today even less harmful that human seasonal flu viruses.

However, several H3N2 strains that are circulating just in pigs and birds could become a much more serious threat if any of them mutated and infected humans.

Sasisekharan and team wanted to find out whether there might be a risk of these purely animal H3N2 strains from re-emerging in humans. If they did, our immune systems would not recognize them as dangerous forms of H3N2.

Four years ago an H1N1 influenza virus strain emerged; it was strikingly similar to the one that killed between 50 and 100 million people in the 1918 pandemic.

Sasisekharan said:

“We asked if that could happen with H3. You would think it’s more readily possible with H3 because we observe that there seems to be a lot more mixing of H3 between humans and swine.”

The team compared the 1968 Hong Kong H3N2 influenza virus strain to about 1,100 H3 strains that are currently circulating in birds and pigs. They concentrated on the gene that codes for the viral hemagglutinin (HA) protein.

The scientists sequenced the genes of HA in five locations that control how viruses interact with infected hosts, and calculated an “antigenic index” for each strain. By doing this they could determine the percentage of these genetic regions that are identical to those of the pandemic strain of 1968, giving them some idea of how easily a flu virus can bypass its host’s immune system.

They also took into account the patterns of the HA protein to glycans (sugar molecules). In order to infect humans, the virus must be able to attach to glycan receptors in human respiratory tract cells.

The team sought an antigenic index of 49% or more and glycan-attachment patterns matching those of the 1968 Hong Kong flu virus. They identified 581 H3 viruses that have the potential to cause a pandemic – and these were just strains that have emerged since 2000. Thirty-two of them came from pigs and 549 from birds.

They then exposed some of the strains they identified to antibodies that were provoked by the current H3 seasonal-flu vaccines. As they had expected, the antibodies did not recognize these H3 strains, so they did not attack them. Sasisekharan said:

“Of the 581 HA sequences, six swine strains already contain the standard HA mutations necessary for human adaptation, and are thus capable of entering the human population either directly or via genetic reassortment.

“One of the amazing things about the influenza virus is its ability to grab genes from different pools. There could be viral genes that mix among pigs, or between birds and pigs.”

The team are now conducting a similar study of H5 influenza virus strains.

Written by Joseph Nordqvist