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 the long terminal repeat (LTR) region and nef in order to investigate associations of viral variation and disease progression, Four long-term survivors who reached 10 years of age or older, and four rapid progressors who survived less than 2 years, participated in this study, LTR sequences of multiple independent viral variants from each individual mere compared, No sequence pattern within the LTR consistently distinguished long-term survivors from rapid progressors or vice versa, Deletions' and insertions within transcription factor binding sites of the LTR and nef ranging from 8 to 341 bp mere found in viral variants from the eldest long-term survivor (LTS047), These deletions and duplications may be associated with the survival of LTS047 via an unknown mechanism, Among all children in this study, the sites in the untranslated region (NF-kappa B, SP1, and TATA box) were more conserved than the sites in the nef/LTR overlap region (NFAT, purine-rich region, USF, TCF1 alpha), reflecting the importance of the sites in the untranslated region for viral replication, A mutation in the E box motif within the USF site among the sequences from a long-term survivor (LTS113) is predicted to disrupt protein binding and may be associated with slow disease progression, Mutations of the SP1-III site in a rapid progressor (RP056) indicate that this site is not necessary for rapid disease progression.