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Human immunodeficiency virus type 1 Vpr: Oligomerization is an essential feature for its incorporation into virus particles

Venkatachari, NJ and Walker, LA and Tastan, O and Le, T and Dempsey, TM and Li, Y and Yanamala, N and Srinivasan, A and Klein-Seetharaman, J and Montelaro, RC and Ayyavoo, V (2010) Human immunodeficiency virus type 1 Vpr: Oligomerization is an essential feature for its incorporation into virus particles. Virology Journal, 7.

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Abstract

HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC) method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection. © 2010 Venkatachari et al; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Venkatachari, NJnjv12@pitt.eduNJV12
Walker, LA
Tastan, O
Le, T
Dempsey, TM
Li, YYAL94@pitt.eduYAL94
Yanamala, N
Srinivasan, A
Klein-Seetharaman, J
Montelaro, RCrmont@pitt.eduRMONT
Ayyavoo, Vvelpandi@pitt.eduVELPANDI
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 9 June 2010
Date Type: Publication
Journal or Publication Title: Virology Journal
Volume: 7
DOI or Unique Handle: 10.1186/1743-422x-7-119
Schools and Programs: School of Medicine > Infectious Diseases and Microbiology
School of Medicine > Structural Biology
Refereed: Yes
Date Deposited: 10 Nov 2016 18:28
Last Modified: 25 Jan 2019 23:55
URI: http://d-scholarship.pitt.edu/id/eprint/30276

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