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. 2017 Oct 20;7:13715. doi: 10.1038/s41598-017-14135-z

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© The Author(s) 2017

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Process of reverse transcription in HIV-1. Panel A, schematic representation of the gRNA with the main genes and the elements constituting the LTR (R, U5 and U3). RNA is drawn in black, DNA in blue. The PBS sequence is indicated by a thicker box, black for RNA and blue for DNA. The central and the 3′PPT RNA sequences are indicated by thicker red boxes. The tRNA^Lys3 used to prime reverse transcription is drawn annealed to the PBS (the extent of the annealed regions throughout the picture is not in scale). Panel B, Minus DNA synthesis is primed by the tRNA and reaches the 5′ end of the gRNA before first strand transfer occurs (dotted arrow) due to the presence of the repeated sequence R. Panel C, this leads to the circularisation of the gRNA and allows the resumption of DNA synthesis. The boxed region is the one that will be drawn in panels D-G. Panel D, synthesis of the (−) DNA strand proceeds generating the first LTR sequence and continues through the internal regions of the genome. 3′PPT and cPPT are resistant to the RNase H cleavage by the RT and prime synthesis of the (+) DNA strand. Panel E, (+) strand DNA synthesis started from the 3′PPT reaches the tRNA^Lys,3, copies the 18 nt at its 3′ end and removes the remainder of the tRNA. This generates + sssDNA and displaces the PBS portion of the gRNA. Panel F, (−) DNA synthesis copies the PBS sequence of the gRNA and degrades it. Panel G, the complementary PBS sequences anneal (second strand transfer) allowing the DNA synthesis to resume. Panel H, (−) DNA strand synthesis displaces the (−) DNA LTR strand ahead (that serves as template for (+) DNA strand) generating one double stranded 5′ LTR. (+) DNA synthesis from the cPPT displaces the (+) DNA strand generated from the 3′PPT and generates the double stranded 3′ LTR. (+) DNA synthesis initiated from the 3′PPT reaches the (+) DNA strand primed by the cPPT and only partially displaces it before stopping definitively at the central termination site, generating the central flap. Panel I, structure of the complete pre-proviral DNA; the LTR sequences are boxed.