Wednesday, January 02, 2013

The birth story of HIV

Hello,

    First of all, Let me Wish a happy new year to all the readers. Its now almost an year, since i have been blogging. And, I can say, to date its been a good experience. I have often posted here, with most happenings in field of research, and sometimes posted more of like a mini-review or rather a snapshot of some data. Today, i decided to make an exception. I thought i had tell you the story of HIV. By story, I don't mean that am going to take you for a ride. I will still stick to science.

   In the 1980's when the first cases of HIV was published, it was thought to be something of rare phenomenon. The disease was strange. It broke the immune defense code of the body leaving it susceptible even to the most simple microbes. And the people infected where men who had sex with men (MSM). And to this day, the etiological agent is one of the most studied and feared infection. So How did it all begin?

Fig 1: Origins of human AIDS viruses
Source
     The Origin of HIV is a big debate. Multiple theories had popped up and some of the theories were competing with each other. However, to date this issue of why has not been resolved fully (Though, Hunter's theory is most accepted and seems to fit the explanation). But, it is now almost beyond a doubt that, the HIV is a derivative of SIV. In simplest words "Daddy of HIV is SIV (simian immunodeficiency viruses)". SIV is a infection found in the monkey group. Almost more than 40 different SIV has been implicated to have crossed the species barrier. Depending on the monkey origin a suffix is used to denote their primate species of origin (e.g., SIVsmm represents sooty mangabeys). As you can see from the figure, there are a variety of HIV that has originated from various sources. And the SIV represents an array of virus and not just a single virus.

     So, i just am intrigued. Who's the grandpa here. In other words, SIV is evolved from? Of course, there is no link of interest to medicine by knowing this. But, yet just as matter of making the story go more alive. The SIV of interest seems probably a hybrid!!! The origins of SIV that lead to HIV traced by a great deal of molecular work . The following is the speculation (With molecular evidence). The first is a virus from Red Capped Mangabey and the other is a virus from Spot Nosed Guenon. Both virus together created a genome hybrid which was stable and turned to evolve to modern day SIV that parented the HIV!!!

    So how did the HIV enter human territory? Seems to be a simple question. At first people were tempted to say zoonotic. That sets a stage for theories- The Polio vaccine theory, Contaminated needle theory, Colonialism theory, Conspiracy theory and Hunter theory. Lets see what each mean.

Photo 1: Edward Hooper
Polio Vaccine theory:

      Oral polio vaccine (OPV) AIDS hypothesis states that an experimental polio vaccine called CHAT, developed at the Wistar Institute in Philadelphia, initiated the Aids pandemic by introducing SIV from the common chimpanzee into some of the million Africans who were given the vaccine between 1957 and 1960. The theory was highly criticized after it made in the form of a book by Edward Hooper (The title of book is "The River"), the main proponent of this theory. The idea was the SIV was introduced into humans with OPV (It was sometimes referred as Hilary Koprowski's vaccine) which was prepared by using kidney cells of infected chimps.

   The theory has multiple flaws. Dr Koprowski testified that primate material used in the vaccine came from Asiatic monkeys, but Hooper reacted "I have individual testimony from three or four people that these chimps were used, the kidneys were excised from these chimps and sent back not only to Philadelphia where Koprowski was working but also to Belgium where they were used in cell cultures." Moreover, Dr Harry Hull, head of the WHO's polio eradication programme says "It also does not make sense in that there were other children who received this vaccine who didn't contract it - so the question is why would it just be the children in the Congo and not elsewhere?". For source and more information go here. Clearly the theory is incomplete or totally wrong. By 2001 Nature and science had published the lack of conclusive evidence. Multiple studies have failed to confirm presence of viral elements specially SIV in the vaccines that has been used. But in 2003, Hooper springs back in action with some new findings. The findings said "In 1950s, virologists in South Africa were using African green monkey cells to amplify the Sabin vaccines, while their colleagues in French West Africa and French Equatorial Africa were apparently using cells from baboons (and perhaps other species, too) to amplify the Pasteur Institute vaccines of Pierre Lepine. In Stanleyville, they had the Lindi chimpanzees". Source.

Contaminated Needle Theory

Photo 2: Preston Marx
Source
    The theory was led by Preston Marx, a virologist in primate research. The theory believed that re-use of unsterile needles, as practiced in Africa in the mid-50s could have spread HIV from person to person. The theory does explain how the HIV might have spread without sexual contact but fails to grasp the origin. The idea sprung from his research findings that the mangabey blood samples tested positive for SIV and that the blood samples from a few of the villagers contained both HIV and SIV genes. As far as research has supported this has been probably a great mode of enhanced transmission but probably origin is blurred. This finding of SIV in villagers blood is better explained with the hunter's theory.

      The main blow to the theory was molecular clock predictions. The prediction was that AIDS would have emerged as a global pandemic in the 1960s as opposed to the 1980s. Ya, at times predictions means nothing. Cause the theory predicts the origin of HIV within ten years of Korbers’ genetic prediction favoring a range from 1915-1941. Impressive!!

Other Competing Theories:

    The Colonialism theory supported by Jim Moore took into consideration the overcrowding, poor sanitation and assumes had first caused immunodeficiency. This allowed time for SIV to become HIV . The spread was enhanced through prostitution. The conspiracy theory or sometimes called as genocidal theory posed in 1985 by Soviet official, Valentin Zapevalov. The theory was believed by many and was thought that it was an artificial creation for biowarfare use. It was further believed that the virus was propagated by small pox vaccine and (or) Hepatitis vaccination trials. These theories doesn't hold much water and lacks some solid evidence back up.

Photo 3: Dr Robert Gallo
Source
Hunter's theory:

    More famously known as the "Cut hunter theory", was laid down by AIDS researcher, Dr. Robert Gallo. The theory suggests that the SIV virus which circulates in African monkey population, was transferred to the people, who hunted the monkeys for their meat (Bushmeat hunting). The virus subsequently was ingested, mutated and emerged as HIV. This gives a chance to explain new strain types emerging and also explains Anti-SIV titers sometimes seen in the village population even to date. The virulent HIV-1 is most possibly derived from the SIV-cpz (Chimpanzee strain) and HIV-2 from SIV-sm (Sooty mangabeys strain). The theory is further supported by many molecular evidence studies and to date has explained most of the observations made in HIV epidemiology.

      So much so for the theories on HIV origin. HIV is a pandemic and has been one of the greatest challenges to the Infectious science. But how as it come to spread to the whole world? The first answer of interest came to be known as "Patient zero".


Photo 4: Gaetan Dugas
Source
      Let me cut the story in short. When a epidemiological investigation was launched to trace source of HIV infections, a large cluster, was seen. The analysis somehow showed a central player with multiple sexual contacts. On deep analysis, he was shown to be the source. The character here is Gaetan Dugas and became infamous as Patient Zero or the index case. It was hypothesized that he had carried the virus from Africa and introduced it to the western world. When he learnt of his disease, (as literature says) he continued to deliberately infect other people, to an estimated 250 people!!! At the time the disease became famous as Gay cancer.

     The story suggests that the evolution of HIV is at about 1950's. But then studies have demonstrated conclusive evidence pointing to existence of HIV strains as early as 1930. This means there is someone before Gaetan to have spread this infection across African regions. By comparing a very large set of HIV isolates, from historical samples a genetic family tree was constructed. The estimates is that the origin dates back to something like 100 years. The best estimates of HIV entering human population is 1908, but it can be as far as 1884.

   So if I can rebuild the story in short it would be something like this. A hybrid SIV circulates in the monkey population. Through a hunter the virus passed on to local human population in western Africa. It slowly spread around through needles and sexual contact which was picked up by exogenous population. The virus transfers through index cases into the western world and spreads through multiple sexual partners throughout the world. Mean while, the virus mutates and evolves establishing itself and come to be the pandemic problem.

ResearchBlogging.org
Auerbach DM, Darrow WW, Jaffe HW, & Curran JW (1984). Cluster of cases of the acquired immune deficiency syndrome. Patients linked by sexual contact. The American journal of medicine, 76 (3), 487-92 PMID: 6608269


Further Reading:

1. Aids and the Polio Vaccine. Link
2. Worobey etal. Direct evidence of extensive diversity of HIV-1 in Kinshasa by 1960. Nature 455, 661-664. Link

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