DOI: 10.1101/483511Dec 4, 2018Paper

Evolution of the HIV-1 RRE during natural infection reveals nucleotide changes that correlate with altered structure and increased activity over time

BioRxiv : the Preprint Server for Biology
Chringma SherpaDavid 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 promotes 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 four nucleotides. In this study, we describe the sequence, function, and structural evolution of circulating RREs in this patient using plasma samples collected over six 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. An increase in RRE functional activity was observed over time, and a key mutation was identified that correlates ...Continue Reading

Related Concepts

Base Sequence
Biological Evolution
HIV Infections
RNA, Messenger
Stem Cells
Virus Replication
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