LTR AND TAT VARIABILITY OF HIV-1 ISOLATES FROM PATIENTS WITH DIVERGENT RATES OF DISEASE PROGRESSION

The genetic heterogeneity and transcription activity of the human immu nodeficiency virus type 1 (HIV-I) LTR region and int gene have been ex amined. Comparison involved the relevant genomic regions of viruses is olated from twenty long-term survivors and from ten typical progressor s. No significant differences were observed in mutation frequencies am ong the two groups, although there was a significant higher proportion of synonymous substitutions in the tat gene of viruses from typical p rogressors. Four LTR sequences showed an insertion of 20-31 residues a t the junction between the LTR Nef-coding and the LTR noncoding region . Neither these insertions nor other genetic changes found in these se quences affected the LTR transcription function, as measured in transi ent expression assays using transfection of both established cell line s and peripheral blood lymphocytes with plasmid DNA. The results did n ot allow the association of structural or functional alterations in LT R or rat with a degree of disease progression. The results reinforce t he concepts of complexity of HIV-1 evolution in infected individuals, and the multifactorial nature of progression to AIDS. (C) 1998 Elsevie r Science B.V. All rights reserved.