6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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High resolution structure of a HIV-1 quasispecies: identification of novel coding sequences.

Int Conf AIDS 1990 Jun 20-23; 6:325 (abstract no. 1047)
Vartanian JP, Meyerhans A, Henry M, Wain-Hobson S; Institut Pasteur Paris, France

OBJECTIVES: To characterize at the structural and functional levels a HIV-1 quasispecies in vivo a high resolution (1%) in order to appreciate the genetic organization of HIV.

METHODS: The first exon of tat was amplified by PCR from HIV-1 proviral DNA derived from fresh PBMC of a CDC stage IV patient. The products were cloned into M13mp18 and 106 recombinants were sequenced. All distinct tat sequences were subcloned into the pSV2gpt expression vector and their activities determined after transfection into SW480 cells.

RESULTS: 31 different variants on tat protein level were found. Amongst those 5 major forms with frequencies of 44%, 11%, 8%, 8% and 5% were identified, they showed comparable activity in the CAT assay. All other 26 sequences were unique. 15 of these which represent 15% of the total proviral population were defective due to in phase stop codon, deletions and single base changes. Interestingly mutation in the start and stop codons of tat, either abolished tat gene expression or created a novel tat/vpu fusion protein.

CONCLUSIONS: This study describes the enormous heterogeneity within HIV quasispecies. At high resolution novel genomes i.e. tat or tat/vpu emerge. While most of these represent defective genomes it may help explaining why all primate and simian lentiviruses do not have the same genetic organization. It illustrates the ease by which HIV may be able to adapt in response to selective pressures and will be able to shed drug resistant genomes.

Keywords: AEGIS, HIV-1, Gene Products, tat, Genes, tat, HIV Long Terminal Repeat, HIV Envelope Protein gp120, HIV Infections, HIV, SIV, Gene Products, vpu, Variation (Genetics), Polymerase Chain Reaction, Exons, DNA Primers, Cats, Animal, Human, genetics, ICA6KWDaegis,hiv-1,geneproducts,tat,genes,tat,hivlongterminalrepeat,hivenvelopeproteingp120,hivinfections,hiv,siv,geneproducts,vpu,variation(genetics),polymerasechainreaction,exons,dnaprimers,cats,animal,human,genetics,ica6

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