AEGiS-11IAC: Adenine clustering, guanine to adenine hypermutation and secondary HIV-1 RNA structure.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Adenine clustering, guanine to adenine hypermutation and secondary HIV-1 RNA structure.

Int Conf AIDS 1996 Jul 7-12; 11:57 (abstract no. Mo.A.1011)
Rabinovich RD, Ghiringhelli D, Gutson D, Fernandez D, Marquina S, Libonatti O; National Reference Centre for AIDS, Paraguay, Argentina. Fax: 54 1 962 5404.

OBJECTIVE: to study the possible relation among adenine accumulation, guanine to adenine hypermutation and RNA secondary structure in HIV-1 genomes.

METHODS: Fifteen HIV-1 and one HTLV-I sequences were obtained from Los Alamos data base. RNA folding (secondary structure) was predicted by using the FOLD program with updated free energy parameters, as implemented in the GCG software package. Fisher's exact test was used to test significance of results. Similar results were found for all HIV-1 strains studied. Only HIV-1MN strain results are shown.

RESULTS: The distribution of codons at which the interchange of G for A would result in a silent mutation was studied in gag, pol and env HIV-1 and HTLV-I gene sequences. For HIV-1 the probability of finding two contiguous codons with A or two with G, in the third position was significantly higher than the expected for a random distribution (p is less than 0.0004). This fact was revealed by patches of A in different regions of the HIV-1 genome but not of HTLV-I. In HIV-1 env gene the highest A/G ratio in the third position of the codon corresponded to the encoding region for the V3 loop. Concerning HIV-1 RNA secondary structure, in regions with preference for A (nucleotides 800-1000, env gene) none of the G to A possible transitions resulted in a lower free energy value. However, in regions of low preference for A (nucleotides 1600-1800), 70% of the G to A possible transitions unstabilized RNA secondary structure (greater than 1.2 Kcal/mol). Besides, in GpA dinucleotide context, the percentage of G in which the transition to A would result in a silent mutation was lower when the 3' nucleotide residue took part in a strong Watson-Crick base pair (G.C).

CONCLUSIONS: In HIV-1, stability of RNA secondary structure could be a restriction for the G to A hypermutation. Moreover, the role of the 3' nucleotide residue (in GpA dinucleotide context) could be explained on the basis of the dislocation mechanism, stabilizing the mismatch produced during retrotranscription. Location of G to A potential transition sites could be important for its implicancies in viral biological properties.

Keywords: AEGIS, Adenine, Guanine, Genes, env, HIV-1, RNA, Cluster Analysis, Codon, HIV, HIV-1 Reverse Transcriptase, Dinucleoside Phosphates, Reverse Transcriptase Inhibitors, Anti-HIV Agents, HIV Infections, classification, genetics, ICA11KWDaegis,adenine,guanine,genes,env,hiv-1,rna,clusteranalysis,codon,hiv,hiv-1reversetranscriptase,dinucleosidephosphates,reversetranscriptaseinhibitors,anti-hivagents,hivinfections,classification,genetics,ica11

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MoA1011

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