Genotypic and phenotypic analysis of a novel 15-base insertion occurring between codons 69 and 70 of HIV type 1 reverse transcriptase

Robert L. Lobato, Eun Young Kim, Ronald M. Kagan, Thomas C. Merigan

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

An HIV-1 isolate possessing a 15-base insertion between codons 69 and 70 of the reverse transcriptase (RT) gene was derived from a patient plasma sample. Investigation of the insertion sequence revealed that this mutation is an ectopic duplication of the first 15 bases of the HIV-1 envelope gene. Phenotypic analysis yielded the following increases in resistance: 371-fold to zidovudine, 84-fold to lamivudine, 32-fold to abacavir, 15-fold to stavudine, 12-fold to didanosine, and 4-fold to zalcitabine. Phenotypic studies suggested that this change does not detract from the overall fitness of the virus. Together, data from this investigation support two conclusions. First, a previously unreported mechanism exists for generating diversity in HIV-1, namely long-distance duplication of genetic material from one portion of the genome to another. Second, large insertions in this region of RT are well tolerated and can confer high levels of resistance to multiple nucleoside analogue reverse transcriptase inhibitors.

Original languageEnglish (US)
Pages (from-to)733-736
Number of pages4
JournalAIDS research and human retroviruses
Volume18
Issue number10
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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