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


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


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


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

Related Concepts

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

KIF1A Associated Neurological Disorder

KIF1A associated neurological disorder (KAND) is a rare neurodegenerative condition caused by mutations in the KIF1A gene. KAND may present with a wide range and severity of symptoms including stiff or weak leg muscles, low muscle tone, a lack of muscle coordination and balance, and intellectual disability. Find the latest research on KAND here.

Regulation of Vocal-Motor Plasticity

Dopaminergic projections to the basal ganglia and nucleus accumbens shape the learning and plasticity of motivated behaviors across species including the regulation of vocal-motor plasticity and performance in songbirds. Discover the latest research on the regulation of vocal-motor plasticity here.