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HIV Envelope Mutations and Onset of AIDS C. Clower, M. Furlong and B. Haidar Background Fifteen HIV subjects were studied in 1998 by Richard Markham’s group. A dataset was generated that contains GP120 clones from the subjects over a period of four years. Results Observation Three subjects experienced an earlier onset of AIDS (within the first 2 years of the study) than the other subjects. Question Is the early onset of AIDS related to the presence of a particular substitution that occurs in the GP120 protein? Example Alignment with Texshade (Biology Workbench) Methods A Clustal W sequence alignment of clones from 3 separate subjects whose CD4 count dropped below 200 after the first 18 months was performed. Clones from the visit prior to the CD4 drop were aligned with the clones from the visit after the CD4 drop. A Texshade was used to identify differences in amino acids between the clones. Sequences from clones prior to the CD4 drop were examined as controls. A BLAST search was used to obtain the PDB file of the GP120 protein. Protein Explorer was used to visualize the crystal structure of GP120 G chain and to identify the positions of the amino acid substitutions that were identified. 4 Onset of AIDS (visit #) 4 11 4 270-175 15 3 250-75 Subject* CD4 Count Substitution Percent of Clones with Decrease Substitution (n) 470-135 RASS NY RK VG 77% (13) 33 % (10) 33% (10) 100% (9) HIV GP120 J Chain structure. Top: Secondary Structure Shown. Bottom: Amino acid substitutions shaded. * Color matches the corresponding amino acids in the structure on the immediate right. Conclusion The positions of all identified substitutions were on the surface of the G chain. Each subject had a unique amino acid substitution that may have led to the early onset of AIDS in these subjects. Future investigations might include a study of the effect of these specific mutations on the GP120 interactions with the CD4 T cell receptor.