Tracing the Footsteps
A Look at Theories on the Origin of HIV
Where Did HIV Originate?Since the discovery of HIV in the early 1980s, one question has yet to be answered: Where did this virus originate? How did it go from being one of the smallest forms of life on record to the cause of the global AIDS pandemic? Many theories have been proposed, everything from the preposterous (HIV was manufactured by the CIA or the KGB and then introduced for the purpose of population control), to the unlikely (HIV originated from a tainted oral polio vaccine in the 1950s), to the academic (that HIV originated by zoonotic transmission from an animal host).
Growing evidence supports the theory that sometime in the not-so-recent past, partners in crime, HIV-1 and HIV-2, jumped the species barrier from primates to humans. The origin of AIDS remains steeped in controversy, due in part to the early stigma attached to HIV and to the racist overtones implicit in linking black Africans to a sexual disease and, indirectly, to primates.
Identifying the natural source of HIV is a difficult process. First, an animal for the virus needs to be found. Second, the geographic distribution of that animal needs to mirror the initial distribution of the disease, in this case West Africa. The virus in the host also needs to have the genetic and structural relatedness to the human virus, and there needs to be a plausible route of transmission of the virus from the animal host to humans.
Evolutionary biologists suggest that simian immunodeficiency viruses (SIV) have lived in parts of Africa for thousands of years. This theory of AIDS as a zoonosis (an infection that can "jump" from species to species) has also been around for quite some time.
However, Beatrice Hahn and her virus detectives from the University of Alabama in Birmingham have recently identified a species of chimpanzee called Pan troglodytes troglodytes that appears to be the "Adam" of HIV-1. Pan troglodytes troglodytes carries a strain of SIV classified as SIVcpz, the closest living relative of HIV.
Why is This Newsworthy All of a Sudden?HIV-1 is a rapidly changing virus that mutates as it reproduces at least a billion times a day in a person's body. Its immediate family tree includes three major groups (M, N and O) and 10 subtypes. New hybrids or "recombinant" viruses mix traits of strains from the two parents, yet like rebellious teens, these viruses develop their own personalities. Each subtype has a distinct genetic profile, so for a vaccine or drug to work, it must know what it's fighting.
There are other issues that arise from a scientific perspective, outside of finding a vaccine.
Research in the area of xenotransplantation (using animal organs, such as pig heart valves, for human transplants) should proceed with caution. Or could you imagine the study of the accidental emergence of an animal virus leading to a new human pandemic? This would not only be a tragedy, but it would end the study of animal transplant research.
I question what awaits us in the jungles of West Equatorial Africa or the rain forests in South America. Have we learned our lesson from HIV? How about Ebola virus? West Nile virus?
As we plow through her jungles and strip away natural resources, maybe Mother Nature is telling us "Get out!" Maybe, by our very presence, we're affecting the natural balance of certain ecosystems.
Let's Look at Measles, for ExampleEach year, hundreds of tourists travel to the mountains of Rwanda in hopes of catching a glimpse of the great ape. According to a report in Primatology, in 1988 the animals began to sneeze and cough, and then die.
Scientists scrambled for an explanation. Eventually, blood and tissues samples were taken that showed the telltale signs of measles infection.
The outbreak appeared to be isolated (tell that to the six dead gorillas and 27 who were left sick), but in retrospect one has to view this as a lesson for impending dangers if we do not proceed with caution. Again, the lesson is that infections can jump from primates to people, or for that matter, from people to primates.
Polio Vaccine TheoryIn The River, Dennis Hooper postulates that AIDS was inadvertently brought on by humans in the early testing of a polio vaccine in Africa in the 1950s. This theory seemed farfetched when it was originally introduced to public attention in a 1992 issue of Rolling Stone. The River suggests that an oral polio vaccine might have been manufactured from contaminated chimpanzee kidney tissue that was subsequently introduced to the African population.
While Hooper's theory has not been proven to have any scientific merit, the time and place of the earliest cases of AIDS and the testing of the vaccine do coincide. From 1957 to 1960, the polio vaccine was given to a million people in what are now Rwanda, Burundi and Congo. This theory challenges Hahn's Pan troglodyte troglodyte zoonotic theory of origin.
If Hooper's theory is correct, the simian ancestor of HIV might have grown in the batches of vaccine used in experimental trial. When the oral vaccine was administered to humans, the simian virus would have passed through a sore and entered the human bloodstream, evolving into HIV-1. From there it would have been transmitted through sexual or blood contact.
In September of this year, Hooper's theory suffered a significant blow. Tests on samples of the vaccine, in storage for over 40 years, showed no trace of HIV or SIV. Studies of mitochondrial DNA from the samples failed to provide any evidence to support the allegations that the polio vaccine had been prepared using chimpanzee tissue.
These results, presented at the Royal Society of London, were a compilation of data conducted at three laboratories in the United States, Germany and France. Evidence from these tests also revealed that the tissue used to prepare this certain vaccine was one of monkey origin, not specifically chimpanzee.
The Wistar Institute (the corporation that manufactured the oral polio vaccine delivered to Africa in the early 1950s) claims that the results not only vindicate its own role in the issue, but also soothe public concern over the safety of vaccines, which had been called into question by the allegations. It should also be noted that the Wistar Institute was responsible for launching these trials independently.
As stated above, there are three major groups of HIV and 10 subtypes that Hahn and her colleagues have documented back to Pan troglodyte troglodyte SIVcpz: an almost exact genetic map to HIV-1. The researchers sequenced a strain of SIVcpz found in a chimpanzee with a natural infection and found that all HIV-1 strains known to infect man are closely related to this SIVcpz lineage.
These researchers also found that HIV-1 group N is a collage of SIVcpzUS and sequences related to HIV-1. This tells us that some "recombination" event happened in the ancestors of a host chimpanzee. Also, HIV-2 has been conclusively proven to have jumped from the primate, sooty mangabey.
HIV is a member of the lentivirus family. A lentivirus is a "slow" virus characterized by a long interval between infection and the beginning of symptoms. This similarity in genome structure made SIVcpz a strong candidate for the origin of HIV-1.
Other characteristics of the virus raised doubts about its role as the precursor to HIV-1. These characteristics included an unexpectedly distant relationship between SIVcpz and HIV-1, a low prevalence of SIVcpz infection in wild-living chimpanzees, uncertain geography between chimpanzee habitats and early AIDS cases, and questions concerning transmission.
In a recent publication, Hahn and her colleagues described SIVcpzUS, a new strain of the SIVcpz virus. When analyzing this strain and comparing previous data, they concluded that the HIV-1 pandemic had arisen as a consequence of SIVcpz transmission from a particular chimpanzee species (Pan troglodytes troglodytes) and presented evidence for a higher number of natural SIVcpz infection based on the discovery of viruses that had recombined.
This suggests that the genetic material from strains of SIVcpz recombined or integrated different genetic material into a new set of genes. They also described the geographic convergence of all groups of HIV-1 (M, N, and O) and SIVcpz from Pan troglodyte troglodytes. The common West Central African practice of "hunting and field-dressing chimpanzees" (i.e., killing, skinning and preparing the meat) was proposed as a likely means of transmission.
Following the VirusThe race is on now to comprehend how and when these viruses made their disastrous leap, and what paths they are currently traveling.
Ask yourself this: If SIVcpz made the leap from chimp to human, what's to stop other viruses from rearing their ugly heads? Think about the impact of emerging retroviruses with a similar latency period and a more virulent clinical manifestation. Combine that possibility with the increased prevalence of "bare-backing," crystal-methamphetamine use, and HIV and hepatitis C co-infection, along with a shift in the demographics of HIV to an underserved minority community.
Emerging infections will not go away. They are a major threat to global health.
Chris Fritzen represented AIDS Project Los Angeles at the recent 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. He is a corporate development officer at APLA and can be reached by calling (323) 993-1565 or by e-mail at cfritzen@APLA.org.
This article has been reprinted at The Body with the permission of AIDS Project Los Angeles (APLA).
This article was provided by AIDS Project Los Angeles. It is a part of the publication Positive Living.