Backtracking the history of the HIV virus through paleovirology

20161027090000, Brenda Lau
What can paleovirology offer to HIV/AIDS?
What can paleovirology offer to HIV/AIDS?
Gliding between the treetops in Southeast Asia, is a rat-bat hybrid-looking animal, with buggy eyes - the Malayan flying lemur. In August this year, Czech scientists have discovered an important trait of this mammal. In its genome, it contains the DNA of the oldest extinct virus that is related to HIV - it is approximately 60 million years old.

This field of research called paleovirology - the study of modern consequences of ancient viruses- takes a broader view in the fight against viruses, besides developing drugs, predicting the spread of the viruses and the quarantine of those infected.

And with this discovery, it was found that the origins of HIV's family of viruses is pushed back by tens of millions of years and scientists can learn how they have changed over time, how viral infection strategies originated and how host immune defences have adapted in response to the changes.

We have lived alongside viruses for millions of years and the study of those relationships could provide insights on how we could fight against them in the future. What more, the retrovirus, is a common type of virus that leaves a mark in its host after infection - weaving its own DNA into the host's chromosomes, which ends up in sperm or eggs and gets inherited by the descendants of the hosts, so the virus becomes "endogenised."

So especially in humans where around 8% of our DNA is viral due to the millions of years of viruses infecting and integrating with the DNA of our ancestors, we become living fossils of ancient and extinct viruses.

Tracing the "endogenising" of HIV

When the HIV/AIDS epidemic emerged in the 1980s, researchers estimated that the lentiviruses could only be a few thousand years old. In 1988, researchers claimed that HIV-1 had evolved from an ancestor, HIV-2, only about 40 years before – in 1940.

Now paleovirologists have shown that those estimates were in fact utterly wrong.

In 2007, lentivirus DNA was found in the genome of the present-day European rabbit by Aris Katzourakis, an evolutionary biologist at the University of Oxford. No one had seen a lentivirus DNA in genomes yet, as many believed that it could not infect the germ line, or it was too young to have left a trace. Initially thought to be contamination, his team found the first endogenous lentivirus.

Two years later, Katzourakis dated the lentivirus, called RELIK, which he found in both European rabbits and hares in the same location, meaning that they were infected around the same time. Since both evolved from a common ancestor, then it meant that RELIK had to be at least as old as their common ancestor - 12 million years.

The search has since broadened and lentiviruses have been found in lemurs and ferrets and the latest, the Malayan lemur. With each new lentivirus, paleovirologists are slowly piecing up the lentivirus lineage and having a clearer picture of how old it is.

So what does it mean for the research of a HIV cure?

The discovery of a HIV-relative that is millions of years old broadens up the research. It also means that a version of the modern HIV epidemic has happened some time ago in early mammals. The virus could have jumped species, infected new hosts, developed immunities or been passed without pathogenic consequences.

“We need to think of the way lentiviruses interact with their hosts, and overcome their host’s defenses, on evolutionary timescales,” Katzourakis said. “Understanding these interactions will be important if we are to eradicate HIV.”

Understanding the evolution of antiviral genes in a host could be the key to the discovery of other drug targets as knowing which antiviral gene and the corresponding lentivirus gene can provide scientists clues to disable it as a therapy for HIV.

Some paleovirologists also study extinct viruses and the proteins they expressed and pair them up against current antiviral genes and figure out how the viruses became extinct and what killed them off.

But it is not strictly antagonistic relationships between a virus and its host. Sometimes exaptation happens, when a host begins to use viral DNA for its own benefit. For example, all mammals have a gene called ENV that has been co-opted from a viral gene and now plays a crucial role in placenta formation. MIMS

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