HIV-1 RNA genome dimerizes on the plasma membrane in the presence of Gag protein
Authors
Chen, JianboRahman, Sheikh Abdul
Nikolaitchik, Olga A.
Grunwald, David
Sardo, Luca
Burdick, Ryan C.
Plisov, Sergey
Liang, Edward
Tai, Sheldon
Pathak, Vinay K.
Hu, Wei-Shau
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyRNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2016-01-12Keywords
Gag–RNA complexRNA genome
RNA-binding protein
retrovirus
virus assembly
Biochemistry
Microbiology
Metadata
Show full item recordAbstract
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.Source
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.DOI
10.1073/pnas.1518572113Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28948PubMed ID
26712001Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1518572113