Scientists confirm HIV theory by sequencing 53-year old tissue

Researchers have extracted a near-complete HIV-1 genome from the lymph node tissue of a man in the Democratic Republic of Congo who has been embedded in wax since 1966.

HIV virusBioMedical | Shutterstock

The nub of tissue, which is around the size of the nail on the pinky finger, was sliced from the 38-year old man who had been fixed with formalin in a protective block of paraffin, with the viral RNA hidden in his lymph node for more than 50 years.

Once freed from its wax casing, the near-complete HIV-1 genome that the team extracted supports the theory that the virus was transmitted to humans from monkeys within the first decade or two of the 20th century.

The genome, which provides a more accurate “molecular clock” for assessing the evolution of HIV, is the oldest example of an almost complete HIV-1 genome to date.

Analysis of the genome has shown that it does not demonstrate an evolutionary timeline that is any different from those generated from more recent samples and dispels the “patient zero” myth – the theory that HIV was introduced to the United States after it was transmitted to a flight attendant.

HIV-1, which is one of the main viruses that causes AIDS, was first discovered in 1983. Older samples containing the genetic sequence of the virus are scarce and their genetic material has usually degraded.

The researchers write:

With very little direct biological data of HIV-1 from before the 1980s, far-reaching evolutionary and epidemiological inferences regarding the long pre-discovery phase of this pandemic are based on extrapolations by phylodynamic models of HIV-1 genomic sequences gathered mostly over recent decades.”

Understanding the origins of the HIV epidemic

The near-complete sequence extracted from this 1966 sample is ten years older than the previous oldest full-length sequence generated.

It provides a glimpse of how the virus looked when it was circulating undetected in central Africa, 15 years prior to a when a string of infections among gay men in the U.S., led to the acknowledgment that a new disease had emerged that researchers eventually called AIDS.

According to lead researcher Michael Worobey and team, calculating exactly when the HIV/AIDS pandemic originated is of great significance because it enables researchers to understand which factors did or did not contribute to the emergence of the causal virus.

Researchers have used the genetic sequences of viruses that infected people in earlier days of the AIDS epidemic to try to estimate when exactly the HIV virus jumped from primates to humans. By comparing differences in the viral sequences, researchers can estimate how long ago the sequences could have diverged from the same source.

This cannot determine when the jump to humans happened, but it can be used to deduce that it had to have been before a particular time.

Previous efforts to pinpoint the precise time of origin have suggested that the virus was introduced to humans during the early 20th century in Central Africa, where once-isolated populations had mixed and merged.

Now, Worobey says the new data suggest HIV probably did not move from primates to humans during the 1920s and Pepin thinks it may even have done so in the late 1800s

Worobey and team say their recovery of the first HIV-1 genome from the 1960s provides direct evidence that the estimates that have been made over the last 50 years are remarkably reliable.

The researchers write:

Analyses did not significantly alter root and internal node age estimates based on post-1978 HIV-1 sequences… And, because this genome itself was sampled only about a half-century after the estimated origin of the pandemic, it empirically anchors this crucial inference with high confidence.”

Worobey, whose team performs virologic archaeology studies on old tissues and blood samples, says the research has involved many years of work: “Just on that sequence, we’ve been plugging away for more than five years.”

Confirming the theory

It should be noted that the work has so far only been posted on the preprint website bioRxiv and has not yet been submitted to a scientific journal or undergone peer review.

However, Oliver Pybus, a professor of evolution and infectious diseases at the University of Oxford, has praised the work, saying that the generation of a genetic sequence from an archived tissue specimen is technically impressive.

“Although its discovery doesn’t substantially alter our current model of the early genetic history of the AIDS pandemic, it does improve our confidence in conclusions previously drawn from modern and partial HIV gene sequences,” says Pybus.

Infectious Disease expert Jacques Pepin (University of Sherbrooke, Quebec) is an author of literature on the history of the AIDS epidemic and is currently working on the second edition of his book “The Origin of AIDS,” which is due to be published late next year. Pepin has called Worobey’s work a “technological feat” and says he plans to factor in the updates in his latest publication.

In conclusion, Worobey and team write: “This unique archival HIV-1 sequence provides direct genomic insight into HIV-1 in 1960s DRC [Democratic Republic of Congo], and, as an ancient-DNA calibrator, it validates our understanding of HIV-1 evolutionary history.”

Journal reference:

Gryseels, S., et al. (2019). A near-full-length HIV-1 genome from 1966 recovered from formalin-fixed paraffin-embedded tissue. bioRxiv. https://doi.org/10.1101/687863.

Sally Robertson

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.

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Comments

  1. nitin saksena nitin saksena Australia says:

    Sally, read your article with great interest, but this is my view that I submitted to Nature and was rejected, but later presented by someone who reviewed my paper. This may sound hypothetical, but an absolute logical truth is there which all of us working on HIV should take a lesson from it and stop looking for HIV organs in primates because they will never find one.
    In so many years we have not been able to find HIV in other mammalian species, simply because all of which have their own immunodeficiency viruses such as Feline immunodeficiency virus (FIV), mouse immunodeficiency virus (MIV), Equine immunodeficiency virus (EIV), Simian immunodeficiency virus (SIV- monkeys, chimps, Gorilla). Tracing the history of these viruses we find that new world monkeys do not have these viruses, suggesting that these viruses came into existence after the continental drift. Moreover, if a virus from old world monkeys is introduced into a new world monkey, they die of AIDS-like disease again suggesting that these NW monkeys die because of lack of adaptation that old world monkeys have developed over many millennia, and the virus has evolved in concert with the host. Also, this further suggests that the old world monkeys must have died of AIDS prior to becoming adapted to SIV.
    Another important point here is that various primate species have their own viruses, and these species maintain very strict sexual segregation, therefore their viruses too show distinct sequences specific to a species, such as Tantalus monkey SIV, Sabaeus monkey SIV, etc., and the list goes on.If such segregation of SIV exists in nature among the primate species, it is highly unlikely a jump has occurred because the virus could not have changed to a sequence we see in HIV today. This is also clear from the HIV-1 genome from the lymph node tissue of a man in the Democratic Republic of Congo who has been embedded in wax since 1966, and it does not change the dogma at all. Also, it needs to be clarified that the interspecies transmission of SIV happens constantly in nature through biting and bruising, but all these primate species in the old world are adapted to-an interesting fact to be noted.
    If you see the natural infection in Regional primate centres where researchers have become accidentally infected with SIV through biting or bruising have shown seroconversion, but have never developed disease. These data have never been published because of the confidentiality.
    Again, taking HIV and putting them into Chimps and other primates do not make them sick. It is the artificial virus SHIV (half HIV and half SIV) that makes them sick. Thus, these two arguments point at one thing that human form of HIV is possibly our own. Retroviral genomes and endogenous retroviruses are a part of human evolution, and these viruses have co-evolved in human gremlin carrying out diverse functions. It is likely that HIV-like virus exited the germline in recent human history, as it did in other mammalian species over many millennia and that is why we have failed to find an HIV-like virus in nature. Human lab experiments in cells have also shown that the Chimpanzee SIV (CIV) cannot infect human cells productively or vice versa. Even though the CIV is closest to the human analogue, it has species-specific attribute to it. It again stresses the fact that immunodeficiency viruses have evolved with the host and are species-specific.
    Hope scientists working on HIV and SIV can take lessons from these natural observations, and initiate a new thinking to look for the origins of HIV. It is long overdue, and because of stale view explored over and over again we have not been able to create a vaccine for HIV.

    Nitin Saksena, Ph.D
    HIV researcher

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News-Medical.Net.
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