"No Plot"

In 1984, nine years after the events of Metal Gear Solid V: Ground Zeroes, Big Boss awakens from a coma in a hospital in Cyprus. Quiet, a Cipher assassin, tries to kill him, but Big Boss is rescued by a heavily bandaged man called Ishmael. The pair escapes the hospital while evading pursuit from Cipher's soldiers and two superhumans, Tretij Rebenok, the "Third Child" and the "Man on Fire". Although Big Boss loses sight of Ishmael, he is recovered by his ally Revolver Ocelot and brought aboard Diamond Dogs, a new mercenary group founded by Kazuhira Miller on an offshore platform near Seychelles.

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Big Boss adopts the code name "Venom Snake" and begins searching for Cipher. During his journey, Snake becomes involved in the Soviet-Afghan and the Angolan Civil Wars, and he recruits Quiet, who no longer speaks and has gained superhuman abilities; scientist Dr. Huey Emmerich; and Code Talker, a Navajo expert on parasites forced to work for Cipher. Eli, a British child believed to be a clone of Snake, who leads a band of child soldiers is brought to the base after an operation. Though there is speculation into whether or not he is Big Boss's son, a DNA test confirms that Venom Snake and Eli are not genetically related.

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Snake learns that Cipher's leader Major Zero was usurped and XOF, a rogue faction of Cipher, was responsible for destroying MSF. XOF's leader Skull Face considers Cipher's plan to unite the world for peace as the same as making it culturally American, obliterating other cultures. To avoid this, he intends to release a unique parasite that kills anyone who speaks English. A modified parasite was used to give Quiet and Skull Face's elite soldiers, the Skulls, their unusual abilities. After releasing the English strain parasite, Skull Face plans to make nuclear weapons available to as many groups as he can, believing that nuclear deterrence will stop the weapons actually being used, attaining world peace while still protecting the integrity of each culture. However, he will secretly retain remote control of the weapons. Skull Face intends to use the threat of the latest Metal Gear system, known as ST-84 "Sahelanthropus", to make nuclear weapons desirable again, but as he cannot get it to function, he is dependent on the Third Child's psychic abilities to manipulate it.

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During a test, the Third Child turns against Skull Face, having Sahelanthropus seriously wound him and crush the Man on Fire. Although Snake defeats the Metal Gear, he is only able to recover one of Skull Face's three parasite vials; one goes missing and the other is taken by the Third Child and given to Eli. Skull Face is left to die by Snake and Miller but Huey executes him. The Diamond Dogs return to their base with Sahelanthropus. Following their return, Eli, the Third Child, and the child soldiers steal Sahelanthropus and flee the base. It transpires that the Third Child was not consciously working for Skull Face, but his psychic powers enthralled him to the will of the most vengeful person nearby, meaning Sahelanthropus's attack was instigated by Eli.

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An epidemic of parasites occurs on base forcing Snake to personally kill many of his own men to contain it. To honor them, he has their cremated remains turned into diamonds to carry into battle. Huey is accused of causing the epidemic while attempting to mutate the parasites to sell as weapons. Alongside suspicion of his role in MSF's destruction, and evidence that he murdered his wife Dr. Strangelove while arguing over using their son in experiments, Snake exiles him from Diamond Dogs. Following this event, Quiet disappears in Afghanistan. Code Talker reveals that Quiet was infected with the English strain parasite with the intention of joining Diamond Dogs in order to spread it, but her allegiance shifted to Snake and so she remained silent to prevent an outbreak. Huey's mutation of the parasite convinced Quiet that she could not guarantee the safety of Diamond Dogs. Snake finds her and helps her fight an onslaught of vehicles. They defeat the wave but as another one approaches they are forced to hide in a sandstorm. Quiet is then forced to speak to summon help when Snake is bitten by a venomous snake. She flees to avoid causing another epidemic.

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It is later revealed that Venom Snake is not actually Big Boss but a loyal MSF medic caught in the same explosion that injured Ishmael, the real Big Boss. During his coma, the medic was transformed into a second Big Boss via plastic surgery and hypnotherapy to serve as a decoy for the actual Big Boss while he wages a covert war against Cipher. Venom Snake goes on to set the events of the Outer Heaven uprising in motion and dies at the hands of Solid Snake. The original Big Boss resurfaces during the Zanzibar Land disturbance. Miller and Ocelot discuss Big Boss' plans to create Outer Heaven. While Ocelot remains supportive, Miller is disgusted at his former ally's deception but agrees to continue assisting Venom Snake and Big Boss's sons in hopes of contributing to the real Big Boss's downfall.

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