In order to better understand the AIDS pandemic, scientists are increasingly looking into its origins. In particular, the ancient hosts of the HIV lineage, the monkeys, are a promising research object. Unlike humans, they apparently live quite well with their viruses. In less than two weeks, the convention center in Toronto, Canada, will be bursting at the seams. Once again, for the 16th time, a great many researchers and a crowd of journalists will gather and hold the International World AIDS Conference. For many more people, however, the results would be vital: At the end of 2005, the World He alth Organization (WHO) estimated the number of people infected with HIV at around 40.3 million people worldwide. 3.1 million died last year alone - and despite intensive research, no cure for the deadly disease has yet been developed.
The regular exchange of experts in such large forums is considered to be correspondingly important. In the scientific part of the conference, one of the main topics is also devoted to the origin and development of the HI virus. The focus is not only on humans, but also on the hosts that the virus used before crossing the species barrier. Because the origin of today's AIDS epidemic, that much is certain, can be found in the thickets of the African jungle, in the bodies of monkeys.
From Vervet Monkey to Human
The HI virus probably found its way to humans about eighty years ago via the chimpanzees of Cameroon. An international research group headed by Beatrice Hahn from the University of Alabama recently discovered that only a few of the native populations of Pan troglodytes troglodytes carry the retrovirus S, which is closely related to the AIDS pathogen according to molecular studies. imian Immunodefiency Virus cpz, SIVcpz for short, in the body.
Chimpanzees often catch a second, distantly related retrovirus - and so the scientists suspect that SIVcpz originated through a recombination of two lentiviruses. One of the great apes could have caught it by eating infected monkeys, a recombinant mixed virus product then at some point, perhaps after being bitten, jumped to the members of the herd. The monkeys, in turn, bit people – or ended up in the stomachs of locals as infectious roasts.
At the end of such a chain of events there were three separate infections in which the immune deficiency disease of chimpanzees spread to humans. Each time, a different variant of HIV-1 emerged in the human victims, including HIV-1 M, the most dangerous of the eleven subtypes of HIV-1 and HIV-2 discovered so far - and the ultimate trigger of the worldwide pandemic .
The pathogen variant HIV-2 also reached humans via monkeys. The carrier here was probably the smoky gray mangabey Cercocebus atys, which is widespread from Sierra Leone to Ghana. Since the fatal virus transmission here occurred in a multitude of separate events, doctors and researchers now distinguish eight subtypes of HIV-2.
Evolution and mutation
However, considering that one bite is usually enough to transmit the immunodeficiency disease pathogen to other monkeys, cross-species infections appear surprisingly limited, write Jonathan Heeney of the Dutch Biomedical Research Center and two colleagues . Only a few mutations made the transition. They had in common, among other things, modified and new regulatory genes, which today are jointly responsible for the aggressive course of the immune deficiency disease.
The respective SIV pathogen only rarely causes AIDS in its original hosts. For example, chimpanzees, smoky mangabeys and also the green monkeys are rather insensitive to their viral load. In contrast to people suffering from AIDS, the armada of CD4 T helper cells in chimpanzees remains largely functional. However, HIV hijacks this immune defense force in the human body so successfully that it is finally overwhelmed and clears the way for all sorts of pathogens and diseases.
Heeney and his colleagues see the reason for these different body reactions in the co-evolution of virus and host. Over time, SIV wiped out or decimated the susceptible animals in the respective monkey species, so that ultimately only those specimens whose genes protected them from the disease were able to reproduce.
Resistant thanks to past plagues?
Such mutations are also known in humans. Among the infected there are those in whom the virus leads to the outbreak of AIDS particularly quickly, as well as those in whom the immune deficiency disease is delayed for an unusually long time. Some resistances are also known. So far, scientists have identified ten different genes and 14 alleles that influence this.
The variants of the CCR5 gene, which encodes a receptor on the surface of immune cells to which the HI virus docks in the event of an infection, have been particularly well researched. Depending on the variant of the gene, this also changes the speed at which the infection spreads in the body. In about ten percent of northern Europeans, researchers even suspect a gene variant called CCR5 delta-32, in which the corresponding receptor is completely missing - an infection with HIV does not occur in these people.
But even after entering the cells, the body can defend itself against the HI virus: With intracellular barriers and enzymatic changes in the structure of the virus, some infected people are able to delay the disease. But where do these people get such defense mechanisms from? The scientists suspect that earlier epidemics played a central role here.
The epidemics of the Middle Ages could have contributed to the gene variant CCR5 delta-32 being able to assert itself. Christopher Duncan and Susan Scott from the University of Liverpool assume that the mutation arose 2,500 years ago and has proved particularly effective against viral infections such as hemorrhagic fever . The body developed the defense mechanisms against HIV long before the new threat even existed.
But this historical development can also be fatal for infected people. Because under the pressure of the immune reactions to the viral attack, HI viruses also help to increase mutations, with which they can get through the mesh of the interception network. For this reason, Heeney concludes, HIV patients often go to war on several fronts because the body has to fight several different strains of the virus at the same time.
Nevertheless, scientists suspect that there could be a stalemate between the two parties over time. Similar to the chimpanzee, humans could then live with their viral load - but then it might also serve as a reservoir which, in the event of an unfavorable chain of events, could produce a new deadly disease.
So even though evolution will provide us with more and more tricks to fight AIDS over time, treating the disease with drugs is the highest priority. Because in order to finally defeat HIV, its possibilities of retreat must also be blocked.