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Journal of Virology, December 2005, p. 14498-14506, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14498-14506.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Analysis of Human Immunodeficiency Virus Type 1 Gag Dimerization-Induced Assembly

Ayna Alfadhli, Tenzin Choesang Dhenub, Amelia Still, and Eric Barklis*

Vollum Institute and Department of Microbiology, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201-3098

Received 3 March 2005/ Accepted 5 September 2005

The nucleocapsid (NC) domains of retrovirus precursor Gag (PrGag) proteins play an essential role in virus assembly. Evidence suggests that NC binding to viral RNA promotes dimerization of PrGag capsid (CA) domains, which triggers assembly of CA N-terminal domains (NTDs) into hexamer rings that are interconnected by CA C-terminal domains. To examine the influence of dimerization on human immunodeficiency virus type 1 (HIV-1) Gag protein assembly in vitro, we analyzed the assembly properties of Gag proteins in which NC domains were replaced with cysteine residues that could be linked via chemical treatment. In accordance with the model that Gag protein pairing triggers assembly, we found that cysteine cross-linking or oxidation reagents induced the assembly of virus-like particles. However, efficient assembly also was observed to be temperature dependent or required the tethering of NTDs. Our results suggest a multistep pathway for HIV-1 Gag protein assembly. In the first step, Gag protein pairing through NC-RNA interactions or C-terminal cysteine linkage fosters dimerization. Next, a conformational change converts assembly-restricted dimers or small oligomers into assembly-competent ones. At the final stage, final particle assembly occurs, possibly through a set of larger intermediates.

* Corresponding author. Mailing address: Vollum Institute and Department of Microbiology, Mail Code L220, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098. Phone: (503) 494-8098. Fax: (503) 494-6862. E-mail: barklis{at}ohsu.edu.

Journal of Virology, December 2005, p. 14498-14506, Vol. 79, No. 23
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.23.14498-14506.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hogue, I. B., Hoppe, A., Ono, A. (2009). Quantitative Fluorescence Resonance Energy Transfer Microscopy Analysis of the Human Immunodeficiency Virus Type 1 Gag-Gag Interaction: Relative Contributions of the CA and NC Domains and Membrane Binding. J. Virol. 83: 7322-7336 [Abstract] [Full Text]  
  • Purdy, J. G., Flanagan, J. M., Ropson, I. J., Rennoll-Bankert, K. E., Craven, R. C. (2008). Critical Role of Conserved Hydrophobic Residues within the Major Homology Region in Mature Retroviral Capsid Assembly. J. Virol. 82: 5951-5961 [Abstract] [Full Text]  
  • Alfadhli, A., Huseby, D., Kapit, E., Colman, D., Barklis, E. (2007). Human Immunodeficiency Virus Type 1 Matrix Protein Assembles on Membranes as a Hexamer. J. Virol. 81: 1472-1478 [Abstract] [Full Text]  


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