Nef and LTR Sequence Variation from Sequentially Derived Human Immunodeficiency Virus Type 1 Isolates

Abstract

Variation in HIV-1 nef and LTR DNA sequences was assessed longitudinally during disease progression in four HIV-1-infected subjects. Point mutations were found among quasispecies obtained at a single time point in each individual, with increasing diversity with disease progression in two of three patients for whom sufficient data were available for analysis. Deletions and rearrangements were more common in late than early stages of disease. Continued sequence evolution in HIV-1 quasispecies with nef deletions along with coexistence of nef-bearing quasispecies suggest that nef-deleted quasispecies are capable of replication in vivo, possibly complemented by quasispecies lacking such deletions and/or by adaptation to a specialized niche within the patients.

Human immunodeficiency virus type 1 long terminal repeat variants from 42 patients representing all stages of infection display a wide range of sequence polymorphism and transcription activity

“…Patterns to LTR variants selected in vivo are suggested by recent studies by Ait-Khaled et al (1,2) demonstrating tissue-compartmentalized phylogenetic clustering of LTR variants in four patients and one patient, respectively. Additionally, McNearney et al (36), in evaluating LTR and Nef variability in four patients longitudinally, found increasing numbers of point and length variants with disease progression as well as greater selective constraint for the LTR sequences than for Nef. All of these studies strengthen the view that conclusions about the importance of specific sequences in the HIV-1 5Ј LTR, if based on the prototype, may not necessarily hold true for naturally occurring LTRs.…”

“…In contrast to longitudinal studies of naturally occurring HIV-1 LTR sequences from a few patients at one stage of disease or one patient throughout a window of disease progression (1,10,11,28,(36)(37)(38), we investigated a cross section of 42 patients at all stages of HIV-1 infection. Here we report on the sequence polymorphism of 478 LTRs, on the transcription activities for a subset of these LTRs, and on altered binding of nuclear factors in vitro to some of the novel in vivo polymorphisms found to correspond with altered transcription.…”

Human immunodeficiency virus type 1 long terminal repeat quasispecies differ in basal transcription and nuclear factor recruitment in human glial cells and lymphocytes

“…As was demonstrated in similar investigations [21,22], most if not all of the nucleotide differences seen between LTRs should be representative of LTR sequences in vivo, and not the product of nucleotide misincorporations during PCR amplification or cloning. As was demonstrated in similar investigations [21,22], most if not all of the nucleotide differences seen between LTRs should be representative of LTR sequences in vivo, and not the product of nucleotide misincorporations during PCR amplification or cloning.…”

Human Immunodeficiency Virus Type 1 Long Terminal Repeat Quasispecies Differ in Basal Transcription and Nuclear Factor Recruitment in Human Glial Cells and Lymphocytes

“…As was demonstrated in similar investigations [21,22], most if not all of the nucleotide differences seen between LTRs should be representative of LTR sequences in vivo, and not the product of nucleotide misincorporations during PCR amplification or cloning. The differences between the patient LTRs and the LAI LTR were of interest because of the uneven distribution of the base pair changes.…”