History
The Legacy Virus was based on a virus created by Apocalypse in the distant future, which was intended to kill the remaining non-mutants. At the time that this alternate version of Apocalypse was killed, the virus had not been perfected, and much like Legacy-3, it targeted all humans indiscriminately. As a result, this virus was never deployed, until Stryfe acquired it and altered it for his own purposes.
During the X-Cutioner's Song crossover, the villain Stryfe gave Mister Sinister a canister that he claimed contained 2,000 years worth of genetic material from the Summers bloodline. When Gordon Lefferts, a scientist working for Sinister, opened the canister after Stryfe was apparently killed by Cable, they found nothing inside. Far worse than that, the canister actually contained a plague, Stryfe's "legacy" to the world.
When Colossus' sister Illyana fell ill and died of the Legacy Virus in Uncanny X-Men #303 (August 1993), he left the X-Men and joined Magneto's Acolytes.
The virus raged on for some time in the mutant population, until Mystique, in an effort to make the world safe for mutants, modified the virus to affect only humans. When Moira found out about this strain of the virus, she finally grasped what the key to the cure was. Unfortunately, she was mortally wounded by Mystique during the Brotherhood of Mutants' attack on Muir Island and did not live to complete the cure. Professor X did manage to telepathically retrieve the critical information before Moira died.
With this information, Beast was able to synthesize the cure a few weeks later, though one that had a price; the virus had first been released by the death of the first victim, and the release of the cure would have the same effect. Colossus, who did not want any more people to suffer his sister's fate, snuck into McCoy's lab and injected the cure into himself and activated his mutant powers, transforming his body into organic steel. This "supercharged" the Legacy cure, simultaneously killing him and stopping the spread of the Legacy virus, instanteously curing even those dying of the virus at that moment (Although it was later revealed Colossus had been resurrected by alien technology and was being used as a test subject for an experimental formula that would reverse mutations before he was rescued by the X-Men).
Unfortunately, this rapid cure had unforeseen geopolitical effects. Thousands of Legacy-infected mutants had been quarantined on the island nation of Genosha, which was controlled by Magneto at the time. The instant cure gave Magneto a vast army overnight and allowed him to begin carrying out his plans for world conquest in the Eve of Destruction crossover.
In X-Factor vol. 3 #10, it was revealed that Singularity Investigations was creating a virus designed to kill mutants. While Jamie Madrox referred to this as the Legacy Virus, it is unclear whether Singularity is actually recreating Stryfe's virus, creating what is to later actually be Stryfe's virus, or merely engineering a new one with a similar purpose.
In X-Force #7, The Vanisher is seen to be in possession of a mutated strain of the Legacy Virus. It was later destroyed by Elixir in X-Force #10.
During the Skrull Invasion of Earth, Beast discovers that the Legacy Virus can infect Skrulls as well. Beast ponders whether to use it against the invading aliens. Cyclops decides to use it to get the Skrulls to surrender.
The Legacy Virus has returned once more as it turned out there were other samples that fell into the hands of Bastion. Samples have been injected into Beautiful Dreamer and Fever Pitch by the Leper Queen in order to cause their powers to go berserk and kill themselves and thousands of humans during an anti-mutant rally held by the Friends of Humanity. It was later revealed that Hellion and Surge were also injected with the Legacy Virus.
Dark Beast is also rumored to have a sample of the Legacy Virus
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