Mechanism of nucleotide incorporation at nontemplated sites by HIV-1 reverse transcriptase

P. H. Patel, B. D. Preston

Research output: Contribution to journalArticlepeer-review


Human immunodeficiency virus type 1 (HIV-1) is highly genetically variable. This is attributed to the error-prone nature of HIV-1 replication and its proclivity for recombinaton. During replication and recombination, reverse transcriptase (RT) must polymerize DNA to the 5′ ends of multiple RNA and DNA template termini while convening HIV-1 RNA to double-stranded DNA. We have determined the fidelity of HIV-1 RT during polymerization to the 5′ ends of HIV-1 long terminal repeat DNA template sequences and to the end of a partial HIV-1 genomic RNA template that mimics a recombination intermediate. We find that HIV-1 RT binds tightly and extends blunt-end duplexes at an efficiency approaching that of recessed-end primers. These products were formed processively via a nontemplated mechanism. While these nontemplated additions are specific for purine nucleotides in incubations containing a single dNTP, highly efficient additions of both purines and pyrimidines are seen in incubations containing all four dNTPs. A molecular model of blunt-end addition is proposed from a structural analysis of HIV-1 RT complexed with primer·template. These observations suggest a potentially important mechanism for retroviral base substitution, small insertions, and small deletion mutations mediated by blunt-end additionand forced copy-choice recombination.

Original languageEnglish (US)
Pages (from-to)126A
JournalJournal of Investigative Medicine
Issue number1
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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