Several million years ago, a virus similar to HIV made its way into the genome of a floating, bulging-eyed lemur, permanently attached.
Trapped in a cage of primate DNA, the virus is no longer able to replicate itself properly or cause life-threatening disease. He became a tamed captive, and the lemur passed it on to his offspring, and from them to their offspring. Today, the benign remnants of this microbe remain Trapped among a fleet of lemur genes—All that remains of a virus may be as deadly as HIV today.
Lentiviruses, the viral group that includes HIV, is an undeniable pest. Viruses cause chronic, slow-fermenting infections in mammals, usually paralyzing a subset of essential immune cells to keep dangerous pathogens at bay. As far as scientists know, these viruses are uniformly destructive to their hosts — or at least, this is true of “all the lentiviruses that we know of,” says Aris Katzurakis, an evolutionary virologist at Oxford University. Which means, a long time ago, the slow lemur virus was likely devastating as well. But somewhere along the way, the conflict between the lemur and the slow virus has dissipated enough that their genomes have been able to mingle. It’s evidence that the slow virus and the host “can coexist, and that peace can be achieved,” says Andrea Kermayer, an evolutionary virologist at Boston College.
Such distincts have been an essential part of mammalian genomic history for thousands of years. Scientists have stumbled across lentiviruses embedded in DNA not only lemurbut rabbitsAnd the nipperAnd the gliding mammals Call cologosand recently rodents—They are all old, all quiet, and all seemingly bereft of their most stressful traits. Infectious versions of those viruses are now extinct. But the fact that they posed an infectious threat in the past could inform the strategies we take against wild lentiviruses now. Finding these extinct lentiviruses tells us about the animals they once harbored, or maybe resident Shelter, active and can transmit it to us. Their presence also indicates that in the struggle between the slow virus and the host, mammals can gain the upper hand. Lemurs, rabbits, ferrets, cologos, and ferrets, after all, are still here. Old lazy viruses are not. Perhaps humans can take advantage of these strange genetic alliances to negotiate similar terms with HIV — or even extinguish the modern virus for good.
When viruses internalize themselves into animal genomes in a genetic manner, a process called endocytosis, scientists generally see it as “sort of wrong,” says Daniel Blanco-Mello, a virologist at the Fred Hutchinson Cancer Center. Once installed in one host, the virus cannot infect others; Much of its genome may end up degrading over time, which is “certainly not what I evolved for.” Fatal errors typically occur with retroviruses, which have RNA-based genomes that they convert into DNA once they enter cells. Reversal allows viruses to attach their genetic material to that of their host, which is then forced to synthesize the proteins of their pathogen along with their own. Sometimes, the retrovirus inadvertently threads itself into the genome of a sperm or egg, and its streaks end up in the offspring of its host. If the fusion does not kill the animal, the former pathogen can become a constant component of the organism’s DNA.
Over time, the human genome has mobilized a horde of these viral wanderers. Our DNA is so full of endogenous retroviruses, ERV for short, that they occupy more space in our genomes than true protein synthesis genes. But in the long list of retroviruses that have crossed our borders, lentiviruses are conspicuously absent, both in our genomes and in those of other animals. Until mid-period, some scientists thought that slow viruses might not be generated Absolutely. It wasn’t quite a precarious idea: lentiviruses have complex genomes, and are highly selective about the tissues they invade; It’s also very dangerous, and not exactly the kind of tenant most creatures would want to occupy their cellular estates. Or perhaps some researchers have assumed that lentiviruses are capable of endogi, but Simply too small. If they had only started infecting mammals during the past hundreds of thousands of years, there might not have been time for such incidents to occur.
Then, about 15 years ago, a team led by Katzorkis and Rob Gifford, an evolutionary virologist at the University of Glasgow, Discovered an endogenous fungal virus called RELIK in rabbit genomes and then in rabbits, an indication that they settled in the common animal ancestor At least 12 million years ago. In an instant, the slow virus timeline stretched, and it continued to grow in the years that followed. Gifford told me that scientists have now identified endogenous lentiviruses in a wide enough range of mammals to suspect that lentiviruses may have been part of our history. At least 100 million years oldGetting into the genomes of our very distant ancestors before the demise of the dinosaurs, before the rise of primates, before kissing the terrestrial masses of North and South America. “This tells us how long the virus and host have been in contact,” Katzurkis told me. During those eons, lentiviruses and the mammals that infect them have been evolving in concert – the pathogen is always trying to infect better, and the animal is always trying to expel its enemy more efficiently.
Knowing that lentiviruses are deeply ingrained in our past can help us understand how other mammals work against those that are still around today. Two species of monkeys, the sooty mangabeys and the African green monkeys, have spent significant evolutionary time with a Lentivirus called SIV – the monkey version of HIV – bred tolerant from him. Even when brimming with viruses, monkeys don’t seem to suffer from the severe immune-impairing disease caused by the pathogen in other primates, says Nikki Clatt, a microbiologist and immunologist at the University of Minnesota. The key seems to be in the monkeys Ultra-resilient and quick-healing courageas well as them immune systems, which launches more silent attacks on SIV, preventing the body from destroying itself during combat. Such immune mockery could eventually enable some retroviruses to reproduce, says Lucy Etienne, an evolutionary virologist at the International Center for Infection Research in Lyon, France.
Many mammals have also developed powerful tools to prevent lentiviruses from reproducing in their bodies in the first place—proteins that can, for example, Chaos with viral entry or replication, or prevent new viral particles from emerging from already infected cells. Viruses can also mutate and evolve, much faster than animals. This gives pathogens plenty of opportunities to counter these defenses. HIV, for example, has no problem evading or penetrating many of the shields that human cells raise against it.
But if we take the equivalent immune defense protein from a monkey, HIV “can’t degrade it,” says Michael Emerman, a virologist at the Fred Hutchinson Cancer Center. Other primates have different infectious histories than ours, which shaped their immune evolution in different ways. Emerman told me that studying the genomes of those primates — or perhaps even the genomes of mammals that carry slow viruses as a neutral genetic cargo — might eventually inspire treatments that “boost our immunity.” At the very least, such experiments could point scientists to the common weak spots of lentiviruses: parts of the virus that immune systems have successfully targeted long enough for their hosts to survive to tell the tale. “Evolution has already taught us the best places to target retroviruses,” says Maria Tokuyama, a virologist at the University of British Columbia. “Why not push for the kinds of interactions we already know worked?”
Another, perhaps more radical idea, may lend itself to HIV treatment: speeding The path toward endocytosis – allowing lentiviruses to entangle themselves in our genomes, hoping to remain permanently, and in a mild manner. “We can figure out a way to silence the virus, so that it’s there but we just don’t care,” says Oliver Fregoso, a virologist at the University of California, Los Angeles. One of the sacred things of HIV research has always been to cook up a vaccine that can prevent infection — which is a very difficult thing to do. But if some kind of nice truce can be found, as Boston College’s Kirmayer tells me, “maybe we don’t need to go that far.”
Cedric Viscott and Sabrina Liddy, virologists at Cornell University, are among those pushing for such an intervention. They take advantage of HIV’s tendency to lie dormant within cells, where it can hide from some of the most powerful antiretroviral drugs. Lydy tells me the virus is “playing dead”, then wakes up again when the coast is clear. But if HIV can be silenced steadilyHer frenzy will end when she crams herself into the genome. “We hope to mimic this natural path taken by retroviruses,” wherever they are Effectively locked in placeLydy said. The imprisoned viruses can then be eradicated from the cells with gene editing.
The idea is ambitious and is still far from offering usable treatments. But if it succeeds, it may result in an additional advantage. After setting up an in-store, our viral tenants can start offering landlord benefits – such as fighting off their energetic relatives. In recent years, researchers have found that some animals, including cats, chickens, mice, monkeys, sheep and even HumansHe was able to co-opt . proteins of some endogenous retroviruses the siege Against incoming viruses of similar likes. Blanco-Melo and Gifford were part of a team that made one like this Discover in 2017, describing the ERV that ancient monkeys may have used to strip virus entries from their cell surfaces. Upon encountering an ERV-ed-up host, the infectious and pathogenic version of this virus can no longer enter.
Finally, “retroviruses are extinct,” Blanco Mello tells me — a finding that he thinks can be attributed to the antics of their spontaneous counterpart. It’s a tricky move, Kiermayer said, and is essentially a way to “turn the virus against itself.” This kind of friendly fire tactic mayo They actually work among the lentiviruses, disappearing into and out of the host’s genome: Species infected with endogenous lentiviruses are usually not spoiled by active lentiviruses, at least none of which have been identified so far, Fregoso told me. With any luck, the same thing could one day be true for HIV, or the virus is more than just a memory — or a dormant part of our cells.