Where did HIV come from

The origin of the killer virus


The origin of the killer virus

By Christina Hohmann


Since AIDS first appeared in the early 1980s, researchers have been trying to understand the origin of the HI virus. Where, when and how did the causative agent of the deadly immune deficiency disease develop? The cradle of the virus is probably in the primeval forests of Africa, with the monkeys.


In the early 1980s, some homosexual men in the United States began developing rare opportunistic infections and tumors. More and more cases occurred and it soon became clear that those affected were suffering from the same disease, the previously unknown immunodeficiency syndrome AIDS. It took only a short time for the Frenchman Luc Montagnier and the American Robert Charles Gallo to identify the human immunodeficiency virus (HIV) as the responsible pathogen. Since the virus was isolated, researchers around the world have been trying to find the source of the AIDS epidemic, which has killed 25 million people to date.


Two different types of the AIDS pathogen, which belongs to the retrovirus family and the lentivirus group, occur in humans: HIV-1 and HIV-2. The majority of those affected around the world carry HIV-1 type M (major), which in turn includes subtypes A to I. On the other hand, HIV-1 type O (outlier) occurs much less frequently. It is almost exclusively limited to Central and West Africa, where it is responsible for around 2 to 4 percent of infections. Another type occurs only in Cameroon, namely HIV-1 N (non-M, non-O). The second strain of retroviruses, HIV-2, is also mainly found in West Africa. It comprises eight subtypes and is significantly less virulent and more difficult to transmit than HIV-1.


Monkeys as natural hosts


According to the current state of knowledge, the human pathogenic HIV strains are derived from immunodeficiency viruses in monkeys. This is supported by strong genetic similarities between the HI viruses and the so-called Simian Immunodeficiency Viruses (SIV). For example, HIV-2 is very similar to the pathogen SIVsm (for Sooty Mangabey) that occurs in smoky gray mangabies (Cercocebus atys). Presumably, the pathogen spread to humans on several occasions through the consumption of infected monkeys, which explains the different subtypes of HIV-2.


It was a little more difficult to trace back HIV-1. Researchers have suspected for a while that chimpanzees are the natural host of the ancestor of HIV-1. A genetic analysis had already shown in 1999 that SIVcpz (for Chimpanzee), the pathogen discovered in captured chimpanzees, was very similar to HIV-1.


To find out whether animals living in the wild also carry the pathogen, researchers working with Beatrice Hahn from the University of Alabama in Birmingham set out on their way to the home of the great apes. In the jungle of Cameroon they collected a total of 446 fecal samples of the chimpanzee subspecies Pan troglodytes troglodytes living there. The scientists discovered antibodies against SIVcpz or RNA of the pathogen in around 35 percent of the samples examined. The monkey antibodies found in 34 samples even reacted with human HIV antigens and provided HIV test results that were as good as those of infected people, the researchers reported in May 2006 in the journal Science (Doi: 10.1126 / science.1126531). By analyzing the sequence of the virus genome, the researchers were able to assign HIV-1 types M and N to different monkey populations. The scientists evaluated their results as proof that the precursor of the HI virus originated from the West African chimpanzees.


The origin of HIV-1 type O remained unclear. It was discovered by researchers working with Martine Peeters from the University of Montpellier. In Cameroon, they collected 378 fecal samples from chimpanzees and 213 faeces from lowland gorillas (Gorilla gorilla gorilla). The analysis of the samples showed that in addition to the chimpanzee excrement, six gorilla samples also gave a positive HIV signal. In the feces, the researchers found a previously unknown strain of the immunodeficiency virus, the SIVgor (for gorilla). According to the sequence analysis, this is the most similar relative of HIV-1 type O to date, the scientists reported in November 2006 in the journal Nature (volume 444, page 164). Since SIVgor were discovered in animals, some of which live 400 kilometers apart, the researchers assume that the pathogen is just as endemic in gorillas as SIVcpz is in chimpanzees. How the gorillas got infected is still unclear. The primates are herbivores and rarely meet chimpanzees in nature. Chimpanzees may have infected gorillas and humans independently, or gorillas may have infected humans after being infected by chimpanzees, Peeters suspects.


Skipped the line


How the virus was able to cross the species barrier and get from apes to humans has not yet been precisely clarified. The most likely theory is that humans became infected when they slaughtered and ate contaminated chimpanzees. Normally the human immune system would have eliminated the pathogen, but in some cases the SI virus may have adapted to the new host and evolved into HIV. Since there are several genetically different HIV strains, the pathogen has probably made the leap across the species boundary on several occasions and developed differently in its new host.


How likely this theory is is shown by the large amounts of monkey meat consumed in Africa. In the Congo Basin alone, according to estimates by the World Animal Protection Society, over a million tons of "bush meat", the meat of wild animals, are marketed. Popular victims are monkeys. Over 20,000 great apes are consumed there every year. In the past 10 to 15 years some species have been almost extinct, such as the red colobus monkey in Cameroon.


But the consumption of bush meat is not only criticized by animal rights activists. Doctors also warn of the risk that other pathogens can enter humans via this route of infection. Obviously, such zoonoses are by no means rare. US researchers found antibodies against the spumaretrovirus SFV, which is normally found in the two primate species mandrill and brazzame cat, in around 1 percent of all villagers in a region close to the jungle of Cameroon ("Lancet" 2004, volume 363, pages 932 to 933). In another tribe in Cameroon, scientists were able to identify a previously unknown, HIV-related retrovirus, which presumably also spread to humans through the consumption of contaminated monkey meat ("Proceedings of the National Academy of Sciences" 2005, Volume 102, pages 7994 to 7999 ).


Early illnesses


It is now considered proven that HIV was transmitted from monkeys to humans. But when did the pathogen make the leap across the species boundary? The earliest known evidence dates back to 1959. A surviving blood sample from an unknown man who lived in Kinshasa (now the Democratic Republic of the Congo) showed antibodies against HIV when examined later.


In 1969, a teenager died of Kaposi's sarcoma in St. Louis, Missouri. Later on, HIV-1 could also be detected in his blood and tissue samples. Early cases also include a Norwegian sailor, his wife and daughter, who all died of AIDS in 1976.


As far as we know today, the first infection with SIV, which developed into HIV, occurred much earlier, presumably as early as the 1930s. This is the conclusion reached by an international team of researchers led by Dr. Bette Korber from Los Alamos National Laboratory. The scientists had developed a complicated computer model with which the evolution of a specific HIV gene could be transferred to a time grid. According to their calculations, the immunodeficiency virus jumped to humans between 1915 and 1941, most likely around 1930, the researchers reported in the science magazine "Science" (volume 288, page 1789). According to the theory, the transmitted SI virus mutated in humans to HIV, which is pathogenic to humans. This was initially limited to a small, isolated population group in West Africa. The pathogen finally spread by 1950 and produced around ten genetic variants. From this time onwards, AIDS slowly developed into an epidemic, although this was not recognized in western countries until 30 years later. The reason for this could be that AIDS only occurred in rare cases and the symptoms of the immune deficiency can vary greatly from person to person.


Resistant monkeys


Unlike HIV in humans, the various SIV strains do not cause immunodeficiency or other symptoms of disease in their natural hosts. More than 30 species of monkeys are currently known that are endemically infected with their own SIV variant and are insensitive to their viral load. They are a popular research object because researchers expect them to provide information about the protective mechanisms that lead to new therapeutic strategies.


So far it was assumed that the animals can keep virus replication under control. But precise analyzes of the viral load showed that the virus replications in monkeys are no different from those in HIV-positive humans. So the animals must have developed other protective mechanisms. Jonathan Heeley from the Biomedical Research Center in the Netherlands suspects that these could have arisen during the coevolution of host and pathogen ("Science" 2006, volume 313, page 462). It could be that HIV and humans will agree on a stalemate in the course of evolution. However, this prospect is of little help in solving today's problems.