The importance of becoming double-stranded: Innate immunity and the kinetic model of HIV-1 central plus strand synthesis

Eric Poeschla

Research output: Contribution to journalReview article

7 Scopus citations

Abstract

Central initiation of plus strand synthesis is a conserved feature of lentiviruses and certain other retroelements. This complication of the standard reverse transcription mechanism produces a transient "central DNA flap" in the viral cDNA, which has been proposed to mediate its subsequent nuclear import. This model has assumed that the important feature is the flapped DNA structure itself rather than the process that produces it. Recently, an alternative kinetic model was proposed. It posits that central plus strand synthesis functions to accelerate conversion to the double-stranded state, thereby helping HIV-1 to evade single-strand DNA-targeting antiviral restrictions such as APOBEC3 proteins, and perhaps to avoid innate immune sensor mechanisms. The model is consistent with evidence that lentiviruses must often synthesize their cDNAs when dNTP concentrations are limiting and with data linking reverse transcription and uncoating. There may be additional kinetic advantages for the artificial genomes of lentiviral gene therapy vectors.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalVirology
Volume441
Issue number1
DOIs
StatePublished - Jun 20 2013

Keywords

  • APOBEC3G
  • Central DNA flap
  • Central polypurine tract (cPPT)
  • HIV-1
  • Innate immunity
  • Lentivirus
  • Nucleic acid sensors
  • Restriction factor
  • Reverse transcription
  • SAMHD1

ASJC Scopus subject areas

  • Virology

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