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Article
HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein
University of Massachusetts Medical School Faculty Publications
  • Jianbo Chen, National Cancer Institute
  • Sheikh Abdul Rahman, National Cancer Institute
  • Olga A. Nikolaitchik, National Cancer Institute
  • David Grünwald, University of Massachusetts Medical School
  • Luca Sardo, National Cancer Institute
  • Ryan C. Burdick, National Cancer Institute
  • Sergey Plisov, National Cancer Institute
  • Edward Liang, National Cancer Institute
  • Sheldon Tai, National Cancer Institute
  • Vinay K. Pathak, National Cancer Institute
  • Wei-Shau Hu, National Cancer Institute
UMMS Affiliation
RNA Therapeutics Institute; Department of Biochemistry and Molecular Pharmacology
Date
1-12-2016
Document Type
Article
Disciplines
Abstract

Retroviruses package a dimeric genome comprising two copies of the viral RNA. Each RNA contains all of the genetic information for viral replication. Packaging a dimeric genome allows the recovery of genetic information from damaged RNA genomes during DNA synthesis and promotes frequent recombination to increase diversity in the viral population. Therefore, the strategy of packaging dimeric RNA affects viral replication and viral evolution. Although its biological importance is appreciated, very little is known about the genome dimerization process. HIV-1 RNA genomes dimerize before packaging into virions, and RNA interacts with the viral structural protein Gag in the cytoplasm. Thus, it is often hypothesized that RNAs dimerize in the cytoplasm and the RNA-Gag complex is transported to the plasma membrane for virus assembly. In this report, we tagged HIV-1 RNAs with fluorescent proteins, via interactions of RNA-binding proteins and motifs in the RNA genomes, and studied their behavior at the plasma membrane by using total internal reflection fluorescence microscopy. We showed that HIV-1 RNAs dimerize not in the cytoplasm but on the plasma membrane. Dynamic interactions occur among HIV-1 RNAs, and stabilization of the RNA dimer requires Gag protein. Dimerization often occurs at an early stage of the virus assembly process. Furthermore, the dimerization process is probably mediated by the interactions of two RNA-Gag complexes, rather than two RNAs. These findings advance the current understanding of HIV-1 assembly and reveal important insights into viral replication mechanisms.

Rights and Permissions
Citation: Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E201-8. doi: 10.1073/pnas.1518572113. Epub 2015 Dec 28. Link to article on publisher's site. Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.
Related Resources
Link to Article in PubMed
Keywords
  • Gag–RNA complex,
  • RNA genome,
  • RNA-binding protein,
  • retrovirus,
  • virus assembly
PubMed ID
26712001
Citation Information
Jianbo Chen, Sheikh Abdul Rahman, Olga A. Nikolaitchik, David Grünwald, et al.. "HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein" Vol. 113 Iss. 2 (2016) ISSN: 0027-8424 (Linking)
Available at: http://works.bepress.com/david_grunwald/25/