The G-virus was discovered in 1988 through the Umbrella Corporation's numerous biological experiments on Lisa Trevor; all of the mutagenic compounds she had been injected with, including the original Progenitor virus and an NE-α Type parasite, had formed into a new virus, which William Birkin dubbed the G-virus. Shortly afterwards, Oswell E. Spencer gave Birkin and his wife Annette permission to initiate the G-virus Project, transferring them to the underground facility under Raccoon City to do so.
In September of 1998, Birkin finally completed and perfected the G-virus, but planned to sell it to the U.S. government instead after a disagreement with his superiors. However, the U.S.S. Alpha team, led by HUNK, showed up on Spencer's orders and gunned Birkin down before taking samples of the virus. Before his death, however, Birkin deliberately infected himself with the G-virus and mutated, taking his revenge on his murderers.
Now a slave to the virus's reproductive instincts, G-Birkin successfully implanted a G-embryo into his daughter Sherry, though Leon S. Kennedy and Claire Redfield managed to treat her with the vaccine before it was too late and subsequently destroy Birkin. Afterwards, Sherry was taken into custody by the U.S. government and subjected to daily tests and experiments under the supervision of Derek C. Simmons, who, unbeknownst to everyone else, worked with his subordinate Carla Radames to secretly use the samples of the G-virus taken from Sherry, along with an enhanced variation of the T-Veronica virus, to create the C-Virus.
In addition, Ada Wong, who survived a near-death experience, retrieved a sample of Birkin's G-virus infected body and narrowly managed to escape Raccoon City before its destruction due to a tip from Albert Wesker.
During the Harvardville Airport Incident in 2005, Curtis Miller was infected with the G-virus by the WilPharma Corporation during his attempts to expose the truth behind the Raccoon City Destruction Incident.
As with its T-Virus, Umbrella considered the G-Virus' primary means of infection to be through injections. To date, only two individuals have been witnessed undergoing primary infection: Dr. William Birkin and Curtis Miller. Unlike creatures created by the t-Virus, "G"s cannot pass infection on to other creatures through physical contact and injury (eg. bites and open wounds).
The secondary infection is drastically-different, and relates to the "G"s' reproductive system. If a "G" decides upon using a human as a breeding tool, they will turn the individual into a host for its embryo through oral-implantation with its reproductive organ, seen on William to be on his hand.
Should the host be of a complementary genetic similarity to the parasite - generally through identical blood groups, as with William and his daughter, Sherry - then a bond between the two will form, leading to the host's assimilation by the parasite, and subsequent mutation into a creature perhaps comparable to the first "G". To date, this occurrence has not been recorded as having happened due to the rarity of G-Virus usage. The only successfully-implanted host with a DNA match - Sherry Birkin - was saved from assimilation by the experimental G-Vaccine, codenamed DEVIL, before mutation could occur with help from her mother, Annette, and Claire Redfield.
In unfortunate cases, a host who has no compatible DNA match will reject the parasite in a matter of minutes. The embryo rapidly grows inside its host before bursting from their chest. Upon exiting the host body, the embryo quickly mutates into its adult form. Brian Irons, police chief of the Raccoon City Police Department, and Monica are the only known victims to suffer this rejection of a G-embryo after being infected by William Birkin.
A primitive form of the virus was discovered in the mutated body of Lisa Trevor, on whom the Umbrella Corporation had been conducting unethical genetic and viral experiments for three decades. When she displayed unexpected immune resistance to the experimental NE-α Type parasite, Birkin and other researchers looked for a cause and found what would later become the G-Virus. The virus was subsequently developed by Umbrella Corporation scientist William Birkin, who had also claimed credit for James Marcus' work on the t-virus.
Alongside work on the G-Virus, Drs. William and Annette Birkin also devised the DEVIL vaccine to suppress the virus' take-over of the body. However, as the vaccine could only be injected into an infectee who still had not succumbed to the virus, its only realistic usage would be the administration of hosts - particularly hosts genetically-similar to the "G". When Sherry Birkin was vaccinated, some aspects of the virus was preserved within her DNA. In the same vein as Lisa Trevor, Sherry developed extraordinary regenerative abilities, though nowhere near what she could have been capable of if left un-vaccinated.