Sunday, May 18, 2003

More on the HIV viruses

Following up on what I said about the HIV viruses last week, I notice that the Economist has an article on HIV-2, the other HIV virus, in this week's issue. Essentially, the article says that new research suggests that the HIV-2 virus crossed over from the species of money called the sooty mangebay twice, once around 1940 and the other time around 1945.

Loosely, viruses evolve over time. If a virus is in the human population then over time the number of variants will steadily increase. If we make some assumptions about the speed of mutation (and better still, have tissue samples contain versions of the virus that are known to come from particular places and times) we can map the evolution and spread of the disease. In particular, we can see when various strains of the virus diverged from each other. If we have two different strains of the virus, and research suggests that they diverged from each other in 1940, say, then there are two possibilities. Either the disease was present in humans before 1940, or the disease was not present in humans until some time after 1940, but it crossed the species barrier on a number of different occasions. If you can find lots of intermediate strains of the virus also present in humans, then this pretty much rules out the second option, unless the species barrier has been crossed on a vast number of different occasions. Presumably the researchers have looked at all strains of HIV-2, and have found that they can trace them all back to having evolved from two common ancestors, but cannot trace them back to any strains intermediate to those two. Hence we have the conclusion that the species barrier was crossed twice for HIV-2.

This compares with the more common (and more contagious and more deadly) HIV-1, which has clearly crossed over into humans at least twice, once in the form of the HIV-1 Group M (for main) virus, that appears to have crossed over from chimpanzees to people in the Congo area, and the HIV-1 Group O (for outlier) virus, that appears to have crossed over from chimpanzees to people in the Cameroon area. We know that Group M was present in Leopoldville (now Kinshasa) in Congo in 1959, because a study of stored blood samples found a positive sample from that time. We believe that Group O was present in 1961 in Cameroon, because a Norwegian sailor who visited Cameroon in 1961 later died of the disease (the earliest known AIDS case), and the virus present in stored tissue samples from his body is consistent with the Group O form of the disease most common in Cameroon today. It seems likely that the disease must have been reasonably common in Cameroon at that time for a foreigner to have become infected (or perhaps he was just extremely unlucky - there was not an AIDS epidemic in Cameroon for a couple of decades after that).

In recent years, researchers have claimed that studies of the differences between various strains of the virus, and knowledge about the speed with which viruses evolve suggests that groups M and O may have crossed over into human beings in the 1940s or even the 1930s. However, the techniques used by such researchers are in some ways problematic. The key question is really how fast do viruses change, and is the speed different in humans than in chimpanzees. The precursor to HIV-1 does not kill chimps. The precursor to HIV-2 does not kill sooty mangabeys. However, when a virus from one species of primate gets transferred into another, then the virus usually is harmful. This tends to suggest that at some point in the past there have been epidemics due to these kinds of diseases in primates, and the primates have evolved so as to become resistant to these particular diseases (or the viruses have evolved not to be harmful to these particular primates, which makes perfect sense, because if a virus's host dies, the virus dies too) and the ultimate consequence has been that we have ended up with primate species with endemic harmless retroviruses.

What am I getting at here? Well, this process is slow. For this to be the case, the viruses must have been present in primates for thousands of years, if not tens or hundreds of thousands of years. The viruses are very well adapted to their host species. They are probably fairly genetically stable, having found an evolutionary niche. Transfer them to another species and they do not have their evolutionary niche any more, and it may be that they have evolved faster. So it may be that the speed of genetic evolution is affected by the species jump, making the uncertainty about when viruses diverged highly dependent on when the species jump actually occurred.

So what do we know? We know for sure that both forms of HIV-1 were present in Africa by the late 1950s. (A third form of the virus, HIV-1 Group N, has recently been discovered also in Cameroon. It seems likely that this form of the virus crossed over later than the other two, although nobody is certain).

What else can we deduce from this? Well, as I said in my previous post, if the viruses have been present in chimp and sooty mangabey populations for thousands of years, there is something remarkable about the fact that species jumps of very similar virus occurred at least three (and apparently five) times in a few decades of the 20th century. This has to do with changed human activity of some kind. I find the frequently argued idea that the transfer occurred via hunting and eating of other primates unconvincing, as this has also being going on for thousands of years, and I find it beyond belief that the species jump never occurred over this period (or that it repeatedly did so without the diseases becoming endemic). The more I read the less convincing I find the polio vaccine theory - the times become less convincing, and the places also become better matched simply with the locations of primate populations rather than the places where polio vaccines occurred. (And there is no evidence that chimpanzee kidneys actually were used in the cultivation of the vaccines). However, something deeply peculiar happened. Mr Hooper is quite right about this. It is quite understandable for the medical establishment to want to blame it on natural causes, but for me to actually believe this, I need a convincing explanation of why AIDS did not become a human epidemic prior to the second half of the twentieth century. If HIV had only crossed the species barrier once, I could believe that it is simply a matter of this being a very unlikely occurrence. If very similar strains of the disease had crossed the species barrier in a short time from the same species, I could believe that the virus had suddenly mutated to make the cross easier. However, similar but different viruses crossed in a very short time. I find this impossible to explain, unless I believe that some new means of transmission suddenly became available to existing viruses. And I don't know what that was.

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