Functional identification of nucleotides conferring substrate specificity to retroviral integrase reactions

Mini Balakrishnan, Colleen Jonsson

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The lung terminal repeats (LTRs) that flank the retrovital DNA genome play a distinct role in the integration process by acting as specific substrates for the integrase (IN). The role of LTR sequences in providing substrate recognition and specificity to integration reactions was investigated for INs from human immunodeficiency virus type 1 (HIV-1), Moloney murine leukemia virus (M-MuLV), human T-cell leukemia virus type 1 (HTLV-1), and human T-cell leukemia virus type 2 (HTLV-2). Overall, these INs required specific LTR sequences for optimal catalysis of 3'-processing reactions, as opposed to strand transfer and disintegration reactions. It is of particular note that in strand transfer reactions the sites of integration were similar among the four INs. In the 3'-processing reaction, sequence specificity for each IN was traced to the three nucleotides proximal to the conserved CA. Reactions catalyzed by M-MuLV IN were additionally influenced by upstream regions. The nucleotide requirements for optimal catalysis differed for each IN, HIV-1 IN showed a broad range of substrate specificities, while HTLV-1 IN and HTLV-2 IN had more defined sequence requirements. M-MuLV IN exhibited greater activity with the heterologous LTR substrates than with its own wild-type substrate. This finding was further substantiated by the high levels of activity catalyzed by the IN on modified M-MuLV LTRs. This work suggests that unlike the other INs examined, M-MuLV IN has evolved with an IN-LTR interaction that is suboptimal.

Original languageEnglish (US)
Pages (from-to)1025-1035
Number of pages11
JournalJournal of Virology
Volume71
Issue number2
StatePublished - Feb 1997
Externally publishedYes

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Integrases
Murine leukemia virus
terminal repeat sequences
Deltaretrovirus
substrate specificity
Substrate Specificity
Nucleotides
nucleotides
lungs
Terminal Repeat Sequences
Moloney murine leukemia virus
Lung
Human immunodeficiency virus 1
catalytic activity
Catalysis
HIV-1
genome
DNA
Genome

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

Functional identification of nucleotides conferring substrate specificity to retroviral integrase reactions. / Balakrishnan, Mini; Jonsson, Colleen.

In: Journal of Virology, Vol. 71, No. 2, 02.1997, p. 1025-1035.

Research output: Contribution to journalArticle

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