Evolution of the HIV-1 Rev Response Element during Natural Infection Reveals Nucleotide Changes That Correlate with Altered Structure and Increased Activity over Time

Journal of Virology
Chringma SherpaD Rekosh

Abstract

The HIV-1 Rev response element (RRE) is a cis-acting RNA element characterized by multiple stem-loops. Binding and multimerization of the HIV Rev protein on the RRE promote the nucleocytoplasmic export of incompletely spliced mRNAs, an essential step in HIV replication. Most of our understanding of the Rev-RRE regulatory axis comes from studies of lab-adapted HIV clones. However, in human infection, HIV evolves rapidly, and mechanistic studies of naturally occurring Rev and RRE sequences are essential to understanding this system. We previously described the functional activity of two RREs found in circulating viruses in a patient followed during the course of HIV infection. The early RRE was less functionally active than the late RRE, despite differing in sequence by only 4 nucleotides. In this study, we describe the sequence, function, and structural evolution of circulating RREs in this patient using plasma samples collected over 6 years of untreated infection. RRE sequence diversity varied over the course of infection, with evidence of selection pressure that led to sequence convergence as disease progressed being found. An increase in RRE functional activity was observed over time, and a key mutation was identified that co...Continue Reading

References

Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M L ZappM R Green
Jan 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·L S TileyB R Cullen
Feb 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·J KjemsP A Sharp
May 1, 1989·Journal of Virology·M L HammarskjöldD Rekosh
Apr 29, 1998·Journal of Virology·Michael BelshanSusan Carpenter
Feb 22, 2003·Immunity·Kevin R BobbittKathleen L Collins
Oct 29, 2003·Journal of Virology·Prasith BaccamSusan Carpenter
Jan 14, 2005·Journal of Medical Virology·Angsana PhuphuakratPrasert Auewarakul
Dec 26, 2008·Proceedings of the National Academy of Sciences of the United States of America·Katherine E DeiganKevin M Weeks
Aug 8, 2009·Nature·Joseph M WattsKevin M Weeks
Mar 17, 2010·Proceedings of the National Academy of Sciences of the United States of America·Michael A DiMattiaJonathan M Grimes
Oct 19, 2010·Nature Structural & Molecular Biology·Matthew D DaughertyAlan D Frankel
Sep 10, 2011·Bioinformatics·Tanja Magoč, Steven L Salzberg
Apr 6, 2012·Journal of the American Chemical Society·Jennifer L McGinnisKevin M Weeks
Apr 27, 2013·Nucleic Acids Research·Stanislav BellaousovDavid H Mathews
May 4, 2013·Nucleic Acids Research·Sabrina LusvarghiStuart F J Le Grice

Citations

Jan 8, 2020·Current HIV Research·Patrick E JacksonM L Hammarskjöld
Jan 11, 2020·Journal of Molecular Recognition : JMR·Nicole G RaadColin A Smith
Sep 2, 2020·Biochemical Society Transactions·Elizabeth C GrayMichelle M Meyer
Apr 1, 2020·Current HIV Research·Chringma SherpaStuart F J Le Grice
Jan 17, 2020·Viruses·Chringma Sherpa, Stuart F J Le Grice
Nov 15, 2020·Nature Communications·Eva-Maria SchneebergerKathrin Breuker

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