Interestingly, C4 has been shown to a cellular substrate of HCV NS3/4A protease and may also contribute to HCV persistence [26] The physiological importance of Factor I is shown by the fact that patients lacking Factor I have increased susceptibility to recurrent infection with encapsulated microorganisms, glomerulonephritis, and rheumatologic diseases [27], [28]. The gene discussed is C4A; the disease is infection.