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

Venkatachari, N.J.; Li, Y.; Le, T.; Tastan, O.; Montelaro, R.C.; Walker, L.A.; Yanamala, N.; Srinivasan, A.; Dempsey, T.M.; Klein-Seetharaman, J.; Ayyavoo, V.

doi:10.1186/1743-422X-7-119

Journal Article

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

Venkatachari, N. J. ; Walker, L. A. ; Tastan, O. ; Le, T. ; Dempsey, T. M. ; Li, Y. ; Yanamala, N. ; Srinivasan, A. ; Klein-Seetharaman, J.FZJ* ; Montelaro, R. C. ; Ayyavoo, V.

2010
Elsevier San Diego, Calif. [u.a.]

Virology 7, 119 (2010) [10.1186/1743-422X-7-119]

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Please use a persistent id in citations: doi:10.1186/1743-422X-7-119

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.

Keyword(s): Amino Acid Sequence (MeSH) ; Cell Line (MeSH) ; HIV-1: chemistry (MeSH) ; HIV-1: genetics (MeSH) ; HIV-1: metabolism (MeSH) ; Humans (MeSH) ; Molecular Conformation (MeSH) ; Molecular Sequence Data (MeSH) ; Protein Structure, Tertiary (MeSH) ; Sequence Alignment (MeSH) ; Virion: chemistry (MeSH) ; Virion: genetics (MeSH) ; Virion: metabolism (MeSH) ; vpr Gene Products, Human Immunodeficiency Virus: chemistry (MeSH) ; vpr Gene Products, Human Immunodeficiency Virus: genetics (MeSH) ; vpr Gene Products, Human Immunodeficiency Virus: metabolism (MeSH) ; vpr Gene Products, Human Immunodeficiency Virus ; J ; HIV-1 Vpr (auto) ; CD28 (auto) ; CTLA-4 (auto) ; IFN-gamma (auto) ; NF-kappa B (auto) ; immune activation (auto)