The HIV gene pol encodes the viral enzymes protease, reverse transcriptase, MG132 DMSO and integrase and represents the most conserved region of the HIV genome. Never theless, differences in the pol sequences inherent to cer tain HIV 1 subtypes have been identified. They include different consensus amino acid residues in the non catalytic regions of the protease, RT and integrase. Some of these Inhibitors,Modulators,Libraries differences are considered to be subtype specific signature sequences, which may poten tially affect drug resistance acquisition and probably replicative capacities of the subtypes, as reviewed earlier. The protease of subtype C is highly conserved and has differences in the AA sequence when compared to subtypes A, B, and D.

The subtype C protease has been shown catalytically Inhibitors,Modulators,Libraries more efficient than the pro tease from B subtype, and capable of recognizing more diverse cleavage sites in its substrates. Bioinformatic analysis of the integrase sequences showed that twelve of fourteen subtype Inhibitors,Modulators,Libraries C specific con sensus AAs are variable within the subtypes. These con sensus residues are located beyond the catalytic triad and functionally important zinc binding motif, LEDGF p75 binding region, and the nuclear localization signal. Recent investigation of the 3 processing and strand transfer activities of the integrase from subtypes B and C, in the presence and absence of the strand transfer inhibitors, did not reveal any differences in these activities and in susceptibility of these enzymes to the inhibitors. RT is an essential enzyme responsible for HIV replica tion and determination of the viral variabilitypoly morphism.

The reverse transcription and related events of the virus life cycle have been thoroughly character ized for subtype B viruses, while much less information is available for subtype C. Despite relative conservation of the RT sequence Inhibitors,Modulators,Libraries among the HIV 1 subtypes, differences in the effect of RT on virus replication, Inhibitors,Modulators,Libraries on frequency and location of background polymorphisms, and on the development of different resistance patterns in response to treatment with RT inhibitors have been observed between subtypes B and C. These differences may reflect the functional diversity of RT between sub types. However, the mechanisms contributing to these differences remain to be determined. In this study, we hypothesize that RT is the major fac tor within the pol encoding proteins responsible for Calcitriol sub type specific differences in the replication of HIV 1. To test this hypothesis, we generated chimeric subtype B and C viruses carrying fragments of the pol gene encod ing the whole RT, distinct domains of RT, and the pro tease or integrase sequences from different subtype C and B isolates.