Viruses 2009, 1(3), 657-677; doi:10.3390/v1030657
Review

Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions

1, 2 and 3,* email
Received: 10 September 2009; in revised form: 28 October 2009 / Accepted: 4 November 2009 / Published: 4 November 2009
(This article belongs to the Special Issue Retroviral Enzymes)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Although polypurine tract (PPT)-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3’ terminus must be accommodated by ribonuclease H (RNase H) and DNA polymerase catalytic centers situated at either terminus of the cognate reverse transcriptase (RT), and in the case of the HIV-1 enzyme, ~70Å apart. Communication between RT and the RNA/DNA hybrid therefore appears necessary to promote these events. The crystal structure of the HIV-1 RT/PPT complex, while informative, positions the RNase H active site several bases pairs from the PPT/U3 junction, and thus provides limited information on cleavage specificity. To fill the gap between biochemical and crystallographic approaches, we review a multidisciplinary approach combining chemical probing, mass spectrometry, NMR spectroscopy and single molecule spectroscopy. Our studies also indicate that nonnucleoside RT inhibitors affect enzyme orientation, suggesting initiation of plus-strand DNA synthesis as a potential therapeutic target.
Keywords: retroviruses; LTR-retrotransposons; polypurine tract; plus strand DNA synthesis; NMR spectroscopy; single molecule spectroscopy; antiviral strategies
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MDPI and ACS Style

Fabris, D.; Marino, J.P.; Le Grice, S.F.J. Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions. Viruses 2009, 1, 657-677.

AMA Style

Fabris D, Marino JP, Le Grice SFJ. Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions. Viruses. 2009; 1(3):657-677.

Chicago/Turabian Style

Fabris, Daniele; Marino, John P.; Le Grice, Stuart F. J. 2009. "Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions." Viruses 1, no. 3: 657-677.


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