The disease was accidentally created at some point after the Augment Crisis. Due to the Klingon Empire's fear of the genetically engineered Human Augments that took over a Bird-of-prey with ease, the Empire decided to create their own version of the enhanced warriors to combat this threat. After examining the wreckage from the captured Bird-of-prey, Doctor Antaak discovered that elements of Augment DNA had survived the vessels destruction. Using the samples they had taken from the genetically modified Human embryos that were left over from Earth's Eugenics Wars, the Klingon scientists attempted to engineer their own super soldiers. However, the results were unexpected as the warriors did develop enhanced strength and intelligence but the superior nature of the Augment DNA began to overwrite the Klingon elements with the resultant warriors having a more Human appearance. While attempting to stabilize the procedure, the doctors found a subject who had suffered from the Levodian flu; something that the researchers were unaware of at the time. The augmentation process resulted in the flu virus being incorporated into the Augment DNA thus creating the Qu'Vat virus. The once carefully controlled experiment thus became a dangerous epidemic that threated the Klingon species with extinction as continued infection resulted in the death of the subject. In order to find a cure for the disease that was destroying their civilization, the Klingon empire attempted to capture Arik Soong in order to procure his aid in creating a cure. However, their attempts had failed due to high security involved in the detention facility where Soong was being held. Thus, the Klingons arranged for Doctor Phlox to be kidnapped by Rigelian mercenaries along with the assistance of Section 31 agents. Phlox was forced to work with doctor Antaak to create a stable variant of the Augment virus. However, Phlox sought to cure the Klingons of the disease, not create Augments for the Empire. Ultimately, he worked on a counter solution which he did not reveal to his Klingon overseers which was curing the disease during the initial stages of augmentation when the cranial ridges disappeared and some minor neural reordering occured but before the fatal neural pathway breakdown. At the same time, the Klingon Empire had authorized containment by any means and ordered Admiral Krell to destroy the infected Qu'Vat colony where Phlox was working. Even after he had found a cure, the Admiral was unwilling to accept it and sought to destroy the Klingon base. However, the intervention of the Enterprise and the Columbia prevented the goal from being achieved. Furthermore, Phlox used a transporter to beam a canister of the virus onto Admiral Krell's vessel thus infecting him and his crew. Thus, Krell ordered his forces to stand down and the cure developed by Phlox was distributed to the infected Klingons throughout the empire. (ENT episodes: "Affliction", "Divergence")
Due to the genetic nature of the virus which had altered Klingon DNA, its affects were passed onto their descendants. Many of those infected had thus lost some of their influence and power within the Klingon Empire. (ENT novel: Kobayashi Maru)
By the 24th century, the effects the virus had on the Klingon race were somewhat forgotten by the general populace of the United Federation of Planets. The virus, carried by Klingon traders, also infected a Trill colony, which created a offshoot race of Trill such as Odan's fourth host. The Klingon Empire had been so embarrassed by the disaster in their failed attempted at genetically enhancing their warriors that they did not discuss it with outsiders and this secrecy prevented non-Klingons from learning of the truth. Klingon warriors in later years would tell non-Klingons that they "don't discuss it with outsiders." (DS9 episode: "Trials and Tribble-ations"; TOS novel: Excelsior: Forged in Fire)
- The virus was named the Qu'Vat virus in the Kobayashi Maru novel.