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dc.contributor.authorLopez-Galindez, Luis Cecilio 
dc.contributor.authorRojas-Cabañeros, Jose Maria 
dc.contributor.authorNajera-Morrondo, Rafael 
dc.contributor.authorRichman, D D
dc.contributor.authorPerucho, M
dc.identifier.citationProc Natl Acad Sci U S A. 1991 May 15;88(10):4280-4.es_ES
dc.description.abstractThe RNase A mismatch cleavage method has been applied to the characterization of natural genetic variation of human immunodeficiency virus (HIV) from different geographical areas. The approach provides a rapid and simple assay for the analysis of differences in closely related viral isolates and allows the establishment of phylogenetic relationships between epidemiologically distinct viruses. Our results show a broad clustering of circulating viruses according to their geographical distribution. We also have analyzed the temporal appearance of mutations associated with the acquisition of resistance to 3'-azido-3'-deoxythymidine (AZT). The results show that mutations in codon 215 of the viral reverse transcriptase can be detected readily by this method in HIV isolates and also directly in peripheral blood from HIV-infected individuals after in vitro amplification of viral sequences with the polymerase chain reaction. The specific recurrence of identical double-nucleotide substitutions in epidemiologically and geographically distant viruses suggests that the restricted amino acid substitutions at this position selected by drug exposure are a critical, rate-limiting step in the acquisition of drug resistance.es_ES
dc.description.sponsorshipWe thankS.Sanchez- Palomino,S.Padilla,A.Bernal,andA.Garcia-Saiz for their excellent help in virus isolation and propagation ;and S.Albaffil,C.Ignacio,P.Ley,and W.Wood for drug susceptibility testing and genotype characterization by PCR.C.L-G. was a fellow from the Fondo de Investigaciones Sanitarias. This work was supported by the Veterans Administration, by Grant PM88-0055 to C.L.G.from the Dirección General de Investigacion Cientifica y Tecnica ,and by Grant CA-33021 to M.P. and Grants AI-29164, AI-30457, AI-27670,and HB-67019 to D.D.R.from the National Institutes of Healthes_ES
dc.publisherNational Academy of Scienceses_ES
dc.subject.meshAcquired Immunodeficiency Syndrome es_ES
dc.subject.meshBase Sequence es_ES
dc.subject.meshCodon es_ES
dc.subject.meshDNA, Viral es_ES
dc.subject.meshDrug Resistance, Microbial es_ES
dc.subject.meshGenes, Viral es_ES
dc.subject.meshHIV es_ES
dc.subject.meshHIV Envelope Protein gp120 es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMolecular Sequence Data es_ES
dc.subject.meshNucleic Acid Hybridization es_ES
dc.subject.meshPolymerase Chain Reaction es_ES
dc.subject.meshViral Core Proteins es_ES
dc.subject.meshZidovudine es_ES
dc.subject.meshGenetic Variation es_ES
dc.subject.meshMutation es_ES
dc.subject.meshRibonuclease, Pancreatices_ES
dc.titleCharacterization of genetic variation and 3'-azido-3'-deoxythymidine- resistance mutations of human immunodeficiency virus by the RNase A mismatch cleavage methodes_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderDirección General de Investigacion Cientifica y Tecnica
dc.identifier.journalProceedings of the National Academy of Sciences of the United States of Americaes_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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