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An RNA Virus that causes deterioration of red blood cells, inflicting a host of bizarre mutations. Humans infected with the C-Virus mutate into B.O.W.s known as J'avo. The C-Virus is able to restore damage to the host's tissue, but in doing so causes further mutation. When these mutations exceed a certain threshold, the host is enveloped in a chrysalid, emerging shortly after as a complete mutation. The C-Virus was developed in the laboratory beneath Tall Oaks cathedral owned by the Simmons family, and the C in C-Virus stands for chrysalid. Based on the T-Veronica Virus used in the Rockfort Island incident in 1998, the C-Virus strengthens and improves the mutagenic effects of its predecessor—an effect which can be seen in the insect and plant-like mutations it induces. Those infected with the C-Virus undergo a self-combustion of sorts upon death due to their abnormally high body temperature; this is also believed to be an effect inherited from the T-Veronica Virus, which gave its victims flammable blood. While an extensive period of cryogenic stasis was necessary for assimilation of the T-Veronica Virus, the C-Virus has successfully overcome virus rejection by the brain cells, and this allows those infected to carry out orders to a certain degree and operate complicated machinery such as weapons and vehicles.

The C-Virus vaccine known as Anti-C was developed using the antibodies found in Jake Muller, who inherited a number of viral-resistant characteristics from his father Albert Wesker and so was unaffected by C-Virus administration. The U.S. government used Jake's blood to manufacture Anti-C, thereby containing the potentially disastrous effects of the outbreak. Administering the vaccine before infection will immunize against the C-Virus, and even those already infected have a chance of survival if the vaccine is administered before J'avo mutation is complete. The vaccine can also immediately neutralize J'avo, chrysalides, and complete mutations. Given the C-Virus's mutagenic properties, however, there is a high chance of the virus itself mutating, and it is only a matter of time before an Anti-C resistant strain evolves.