Limited nucleotide changes in the rev response element (RRE) during HIV-1 infection alter overall rev-RRE activity and rev multimerization

Emily A. Sloan, Mary F. Kearney, Laurie R. Gray, Kathryn Anastos, Eric S. Daar, Joseph Margolick, Frank Maldarelli, Marie Louise Hammarskjold, David Rekosh

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

HIV-1 Rev and the Rev response element (RRE) enable a critical step in the viral replication cycle by facilitating the nuclear export of intron-containing mRNAs, yet their activities have rarely been analyzed in natural infections. This study characterized their genetic and functional variation in a small cohort of HIV-infected individuals. Multiple Rev and RRE sequences were obtained using single-genome sequencing (SGS) of plasma samples collected within 6 months after seroconversion and at a later time. This allowed the identification of cognate sequences that were linked in vivo in the same viral genome and acted together as a functional unit. Phylogenetic analyses of these sequences indicated that 4/5 infections were founded by a single transmission event. Rev and RRE variants from each time point were subjected to functional analysis as both cognate pairs and as individual components. While a range of Rev-RRE activities were seen, the activity of cognate pairs from a single time point clustered to a discrete level, which was termed the set point. In 3/5 patients, this set point changed significantly over the time period studied. In all patients, RRE activity was more sensitive to sequence variation than Rev activity and acted as the primary driver of the cognate set point. Selected patient RREs were also shown to have differences in Rev multimerization using gel shift binding assays. Thus, rather than acting as a simple on-offswitch or maintaining a constant level of activity throughout infection, the Rev-RRE system can fluctuate, presumably to control replication.

Original languageEnglish (US)
Pages (from-to)11173-11186
Number of pages14
JournalJournal of Virology
Volume87
Issue number20
DOIs
StatePublished - 2013

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response elements
Response Elements
Human immunodeficiency virus 1
HIV Infections
HIV-1
Nucleotides
nucleotides
infection
Infection
genome
Cell Nucleus Active Transport
Viral Genome
seroconversion
virus replication
Introns
Sequence Analysis
introns
Gels
gels
HIV

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Limited nucleotide changes in the rev response element (RRE) during HIV-1 infection alter overall rev-RRE activity and rev multimerization. / Sloan, Emily A.; Kearney, Mary F.; Gray, Laurie R.; Anastos, Kathryn; Daar, Eric S.; Margolick, Joseph; Maldarelli, Frank; Hammarskjold, Marie Louise; Rekosh, David.

In: Journal of Virology, Vol. 87, No. 20, 2013, p. 11173-11186.

Research output: Contribution to journalArticle

Sloan, EA, Kearney, MF, Gray, LR, Anastos, K, Daar, ES, Margolick, J, Maldarelli, F, Hammarskjold, ML & Rekosh, D 2013, 'Limited nucleotide changes in the rev response element (RRE) during HIV-1 infection alter overall rev-RRE activity and rev multimerization', Journal of Virology, vol. 87, no. 20, pp. 11173-11186. https://doi.org/10.1128/JVI.01392-13
Sloan, Emily A. ; Kearney, Mary F. ; Gray, Laurie R. ; Anastos, Kathryn ; Daar, Eric S. ; Margolick, Joseph ; Maldarelli, Frank ; Hammarskjold, Marie Louise ; Rekosh, David. / Limited nucleotide changes in the rev response element (RRE) during HIV-1 infection alter overall rev-RRE activity and rev multimerization. In: Journal of Virology. 2013 ; Vol. 87, No. 20. pp. 11173-11186.
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