A reader (hat tip, sandy) has pointed me to a very interesting interview with CDC’s chief virologist, Ruben Donis, in Science Magazine’s blog, ScienceInsider. In it he provides further information on the confusing reports about the species origin of the current swine flu, originally said to be of swine, human and bird origin but later claimed to be only swine. It may be that both are true, depending on how you look at it.
According to Donis, who has been sequencing the isolates, the virus is all recent swine but bears the marks of human and avian ancestry in some genes. Different genes have different close relatives. Influenza genes make 11 proteins but are packaged into eight discrete segments. The HA, NA and matrix proteins are the ones seen most readily by the immune system, but there can be an immune response to the protein products of any of the genes. Donis said in his analyses the HA gene (the H-part of H1N1) is equidistant on the family tree of swine flu viruses from those that circulate in the US and Asia/Europe, hanging out on a “lonely branch” all by itself. In other words, it doesn’t have any evidence close swine relatives. The NA and matrix genes have close relatives, all swine. So where are the human and bird genes?
Starting in 1918, when it was thought we gave pigs our influenza viruses from the pandemic, all swine viruses in the US were H1N1 viruses. Suddenly, in 1998 that switched to H3N2 and caused large outbreaks of swine flu in the midwest. Why did this happen all of a sudden? H3N2 refers to subtypes of HA and NA on the surface of the viral particle. There are proteins inside the virus, too, and inside there were differences. The PB1 gene, like the H3 and N2, were human. The PA and PB2 genes (involved in viral replication machinery) were bird origin. The remaining genes were typical pig viruses seen in North America. So this was a triple reassortant (swine, human, bird). At the moment we don’t know where or when or how this happened ten years ago, but the new combination was considerably more fit than the H1N1 and soon crowded it out. In effect, the pigs had a “pandemic” (more accurately, a North American panzootic) with H3N2. So is this a pig virus or a human-pig-bird virus or what?
Q: How does it tie to the current outbreak?
R.D.: Where does all this talk about avian and human genes come from? I was describing a fully swine virus. For [the] last 10 years, this has been a fully swine virus. Can you tell I have an accent? I?m a U.S. citizen but I have the roots in Argentina. It?s like me. I?ve been in the U.S. since 1980. I?m a U.S. citizen but I have an accent. (Jon Cohen interview with Ruben Donis, ScienceInsider)
The novel members of the curren swine flu constellation seem to be the swine origin NA and matrix proteins with an Asian-like lineage. How did they get here? Donis points out that North American viruses were actually exported to Asia when many countries imported US swine flu. Asian and European swine viruses have already mixed a fair amount so they are referred to as the Eurasian lineage. So that might explain how the North American swine segments (with the human and avian parts since 1998) got to Asia. How did they get back here? The return trip was not necessarily made via a pig. It could have been a person. We don’t know. But Donis doesn’t think the mixing happened in Mexico, but the phylogenetically isolated HA gene isn’t very informative as to where.
What about the Veracruz pig farm (Smithfield Farms)?
Q: What do you think about the pig farm in Veracruz?
R.D.: I don?t know the details. They said they had a huge operation and the workers were not getting sick; that?s what the company claims. The only suspicious thing in that story is this is the largest farm in Mexico. The fact that the index case also is from the area makes it interesting.
Q: Do large farms have more swine flu?
R.D.: Not really. Even folks who have 50 pigs have to buy feed and supply from vendors that go from farm to farm, and they don?t wash their boots or whatever. Usually the virus is transmitted very effectively.
How concerned is CDC’s chief virologist?
Q: What do you think of this outbreak?
R.D.: This is the first one I?ve seen firsthand as a virologist. The avian influenza outbreak is not comparable because this is unfolding so quickly. This reminds me of SARS. With avian there?s very little transmission. And even with SARS, transmission was far less.
Q: Does this one scare you?
R.D.: I saw figures that do scare you. We?ve received 300 samples from Mexico, and these cover the span of February, March, and April. And you look at flu A, traditionally it?s A/H1 or A/H3 or it’s B up until the end of March. There are two or three cases up to [the] last days of March that are swine. Then in April they skyrocket. So all the cases in the D.F. areas [Mexico City], where most samples came from, it really transmits very efficiently.
Q: What is the date of first sample?
R.D.: I think it?s the end of March, the first positive specimen.
Q: Did Mexico react quickly enough?
R.D.: They didn?t know. They probably thought it was regular flu.
This is a very interesting interview and ScienceInsider seems to have some good sources. Recommended.