Our longitudinal analysis of alternative coreceptor usage which suggests an improvement in the ability of R5 Envs to use CCR3 and FPRL1 as alternative coreceptors at late stage infection, and our mutagenesis studies which suggest a critical role for the V3 loop crown in the functional linkage between CCR5/FPRL1 usage, provide additional insights into how R5 C-HIV Envs may evolve in vivo and contribute to C-HIV pathogenesis. The gene discussed is CCR5; the disease is infection.