LONG TERMINAL REPEAT AND NEF GENE VARIANTS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN PERINATALLY INFECTED LONG-TERM SURVIVORS AND RAPID PROGRESSORS

HIV-1 sequences from perinatally infected children were analyzed in th e long terminal repeat (LTR) region and nef in order to investigate as sociations of viral variation and disease progression, Four long-term survivors who reached 10 years of age or older, and four rapid progres sors who survived less than 2 years, participated in this study, LTR s equences of multiple independent viral variants from each individual m ere compared, No sequence pattern within the LTR consistently distingu ished long-term survivors from rapid progressors or vice versa, Deleti ons' and insertions within transcription factor binding sites of the L TR and nef ranging from 8 to 341 bp mere found in viral variants from the eldest long-term survivor (LTS047), These deletions and duplicatio ns may be associated with the survival of LTS047 via an unknown mechan ism, Among all children in this study, the sites in the untranslated r egion (NF-kappa B, SP1, and TATA box) were more conserved than the sit es in the nef/LTR overlap region (NFAT, purine-rich region, USF, TCF1 alpha), reflecting the importance of the sites in the untranslated reg ion for viral replication, A mutation in the E box motif within the US F site among the sequences from a long-term survivor (LTS113) is predi cted to disrupt protein binding and may be associated with slow diseas e progression, Mutations of the SP1-III site in a rapid progressor (RP 056) indicate that this site is not necessary for rapid disease progre ssion.