HIV initiation of reverse transcription

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How should I start? HIV initiation of reverse transcription

When HIV enters the human cell, the first challenge it faces is turning its genetic material into a more stable copy. This process is named reverse transcription. To initiate this process there are both viral and human factors that need to come together in a synchronized three-dimensional moving puzzle.

Recent studies from the Puglisi lab solved several cryoEM structures of the reverse transcription complex and captured the elusive early initiation steps. In addition, the researchers used elegant biochemistry and single molecule FRET to study the dynamics of the process. They used a 101 mer of the viral RNA to provide us with the first glimpse of the reverse transcription complex in the context of a larger viral RNA. The results reveal how the structure of the viral RNA forms energetic barriers that hinder and precisely regulate the progression of the reverse transcriptase enzyme.

To read more, check out these 3 papers describing the +1 step, +3 steps, and a review of reverse transcription initiation:

  1. Architecture of an HIV-1 reverse transcriptase initiation complex
    Larsen KP*, Mathiharan YK*, Kappel K*, Coey AT, Chen DH, Barrero D, Madigan L, Puglisi JD, Skiniotis G, Puglisi EV
    Nature, 2018, 557 p. 118-122
    link
  2. Distinct conformational states underlie pausing during initiation of HIV-1 reverse transcription
    Larsen KP*, Choi J*, Jackson LN*, Kappel K, Zhang J, Ha B, Chen DH, Puglisi EV
    Journal of Molecular Biology, 2020, 432(16) p. 4499-4522.
    link.
  3. Advances in understanding the initiation of HIV-1 reverse transcription
    Krupkin M*, Jackson LN*, Ha B*, Puglisi EV.
    Current Opinion in Structural Biology, 2020, 65 p. 175-183.
    link.

Love HIV reverse transcription initiation? Follow the team on twitter: @LNJackson7, @KalliKappel, @_Choi_Junhong, @DagsDoesScience, @YMathiharan, @LabSkiniotis, @puglisilab, and you can find me at @MiriKrupkin!

See you soon, Miri