AEGiS-12IAC: Diversity of HIV-1 long terminal repeat (LTR) sequences derived from Mexican donors at different stages of infection.

12th International AIDS Conference

Geneva, Switzerland - June 28-July 3, 1998

Diversity of HIV-1 long terminal repeat (LTR) sequences derived from Mexican donors at different stages of infection.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:11-2 (abstract no. 11148)

Soler Claudin C, Gomez Roman VR, Basualdo Sigales MC
Unidad De Investigacion En Retrovirus H, Facultad de Quimica, SSA, Mexico, D.F., Mexico.

OBJECTIVE: To examine the variability of the HIV-1 Long Terminal Repeat's (LTR) derived from 17 patients at different stages of HIV-1 infection.

METHODS: Nested-PCR primers were designed to amplify fragments of the HIV-1 LTR from peripheral blood samples donated by 17 patients. LTR amplicons were purified and cloned into pUC18 bacterial vectors. The resulting LTR clones were sequenced with a conventional dideoxy-termination protocol.

RESULTS: LTR amplicons were obtained from all patients (100%). A total of 115 LTR-plasmid clones, designated pUC18, HIV-1, LTR, Mex, were fabricated. To date, sequence analysis of clones has revealed the following: (i) a large, 226 base-pair deletion in the overlapping nef-LTR region derived from patient Mex.LTS10, a Mexican slow progressor with over 10 years of infection and a high CD4+ T cell count (> 500 cells/mm³); (ii) an 18 base-pair deletion within one of the binding sites for the nuclear factor of activated T cells (NFAT-1) in an LTR clone derived from a second patient, Mex.LTS11 (CD4+ T cells < 500/mm³); and (iii) multiple point mutations in all four LTR sequences when compared to prototypic HXB2/pNL43 HIV-1 clones. Interestingly, in spite of numerous attempts throughout the last two years, HIV-1 has not been isolated from peripheral blood mononuclear cells (PBMC) derived from Mex.LTS11, whereas virus has been repeatedly isolated in vitro from the other 16 patients included in the LTR genotypic analysis.

CONCLUSIONS: We have identified a Mexican slow progressor harbouring an HIV-1 quasi-species with a major 2.26 bp deletion in the overlapping nef-LTR region of the proviral genome. However, the presence of this deleted quasi-species in his PBMC does not affect the overall ability of HIV-1 to be isolated from the peripheral blood of this patients. In contrast, a smaller 18 bp deletion within one of the NFAT-1 binding sites of the LTR may explain our inability to isolated HIV-1 from the peripheral blood of another patient.

Keywords: AEGIS, HIV Long Terminal Repeat, Terminal Repeat Sequences, HIV-1, HIV Infections, CD4 Lymphocyte Count, Transcription Factors, DNA-Binding Proteins, CD4-Positive T-Lymphocytes, transcription factor NF-AT, In Vitro, Human, genetics, ICA12
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