Influenza: It's all in the genes

May 4, 2009

It took a perfect storm of circumstances for the latest influenza outbreak to occur, says a Texas AgriLife Research scientist.

There's nothing new about H1N1 influenza, says Dr Jason Osterstock, an AgriLife Research infectious disease epidemiologist. In fact, the latest human flu vaccine and most all flu vaccines for humans and swine include a strain of H1N1, which is considered the most common of the human and swine influenzas.

It just wasn't the right H1N1. It couldn't have been, because this combination of H1N1, when broken down to its very core - the nucleic acids that make up the virus - has never been identified before, Osterstock said.

Viruses can be ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) based, he said. Those that are RNA-based, like influenza, may change or mutate rapidly and swap genetic material, as is the case of this latest outbreak.

The differences in the genetic make-up of the virus are what make flu viruses differ in terms of what species they affect, how severe the symptoms are and how effectively they may be spread, Osterstock said.

This latest virus has been identified as having gene segments from human, swine and avian virus strains, he said.

One way to determine if a person exhibiting flu-like symptoms has the latest flu of concern is to look at specific gene sequences and match them to other cases, Osterstock said.

There are basically three steps to doing that, he said. Influenza is broken into three broad groups: A, B and C, based on the molecular properties. Typically, types A and B are both found in humans, while pigs only have type A; type C is much less common in both species. These determinations can be and are made at the local doctor or clinic level using rapid flu tests.

This influenza is a type A, but within type A are a lot of possible strains (or subtypes), because it includes combinations of two proteins: hemagglutinin and neuraminidase, Osterstock said.

There are 16 different hemagglutinin and nine different neuraminidase proteins, he said. This is where the H1N1 designation is made, depending on which hemagglutinin (H) and neuraminidase (N) proteins are contained in the virus. That is determined by an official state laboratory.

But to determine if it is a positive match for the latest "pandemic-like" flu, another step has to be taken, looking at the gene sequence, Osterstock said. This is primarily done by the Centers for Disease Control and Prevention, and a positive match will verify that the virus matches the human, swine and avian combination strain of concern.

"I want to emphasize that we need to understand when we call it H1N1 or influenza A, we're still talking about a lot of viral strains that make up those classifications," he said. "We hear the use of the singular name, such as swine flu, obviously because it is easy, but its not really the whole story."

While H1N1 is the most common of swine influenzas, Osterstock said, swine also have H1N2, H3N2 and H3N1 types. And humans have H1N1 influenzas. Importantly, influenza viruses can be transmitted from humans to swine or from swine to humans, fostering scenarios where genes from different strains can mix.

"So when you see a strange new flu virus, it is possible somewhere it had a pig as a host, particularly if genes consistent with a pig strain are present," he said. "The question of when this combination took place, however, would be a very difficult one to answer. It could have been four years ago or four days before the outbreak."

And it would not have likely involved just one pig, one bird and one human, Osterstock said. It would have involved infections within and among populations of each of these species when the crossing or shifting of the genes took place.

"After it entered the human population, it could have changed several times before becoming the virus we observe today, able to be transferred between people with, apparently, some efficiency," he said. "That's why it would be hard to ever track it back to an exact source."

Osterstock said it was a perfect storm of situations: it had to have the right combinations of genes, cause sufficient disease and symptoms to spread, contact had to overlap - a lot of things had to fall in place for this situation to occur.

"Although there are some things we do know about this virus, such as the fact that you cannot get infected by eating pork or that symptoms and preventive measures are similar to seasonal flu, there is still a lot to learn," Osterstock said.

The flurry of research activity worldwide associated with this influenza strain will help to address important issues regarding whether it can infect swine or other animals, development of effective vaccines and details regarding its evolution, he said.