Structure-functional analysis of human immunodeficiency virus type 1 (HIV-1) Vpr: role of leucine residues on Vpr-mediated transactivation and virus replication

Virology
Dineshkumar ThotalaV Ayyavoo

Abstract

HIV-1 Vpr has been shown to transactivate LTR-directed expression through its interaction with several proteins of cellular origin including the glucocorticoid receptor (GR). Upon activation, steroid receptors bind to proteins containing the signature motif LxxLL, translocate into the nucleus, bind to their response element, and activate transcription. The presence of such motifs in HIV-1 Vpr has prompted us to undertake the analysis of the role of specific leucine residue(s) involved in Vpr-GR interaction, subcellular localization and its effect on Vpr-GR-mediated transactivation. The individual leucine residues present in H I, II, and III were mutated in the Vpr molecule and evaluated for their ability to interact with GR, transactivate GRE and HIV-1 LTR promoters, and their colocalization with GR. While Vpr mutants L42 and L67 showed reduced activation, substitutions at L20, L23, L26, L39, L64, and L68 exhibited a similar and slightly higher level of activation compared to Vprwt. Interestingly, a substitution at residue L22 resulted in a significantly higher GRE and HIV-1 LTR transactivation (8- to 11-fold higher) in comparison to wild type. Confocal microscopy indicated that Vpr L22A exhibited a distinct condensed nuclear l...Continue Reading

References

May 1, 1992·The Journal of Experimental Medicine·J P NorthropP S Mattila
Jun 1, 1990·Journal of Virology·E A CohenW A Haseltine
Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·S MahalingamA Srinivasan
Jul 19, 1994·Proceedings of the National Academy of Sciences of the United States of America·N K HeinzingerM Emerman
May 14, 1996·Proceedings of the National Academy of Sciences of the United States of America·H HtunG L Hager
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·A GervaixJ Corbeil
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·L K FelzienG J Nabel
Jan 5, 1999·The Journal of Experimental Medicine·T KinoG P Chrousos
Jun 29, 2002·Molecular Endocrinology·Donald B DeFranco
Mar 5, 2003·Journal of Molecular Biology·N MorelletB P Roques
Mar 19, 2003·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Parithosh K TungaturthiAlagarsamy Srinivasan
Mar 19, 2003·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Tricia H HoganBrian Wigdahl

❮ Previous
Next ❯

Citations

Mar 2, 2011·The Journal of Biological Chemistry·Eugene Boon Beng OngHiroyuki Osada
Feb 9, 2012·The Indian Journal of Medical Research·Ujjwal NeogiAkhil C Banerjea
Oct 11, 2016·Scientific Reports·Ann BaeyensBruno Verhasselt
Mar 11, 2009·AIDS Research and Human Retroviruses·Bizhan RomaniSusan Engelbrecht
Jun 6, 2014·Journal of Virology·Sakshi AroraAkhil C Banerjea
Nov 17, 2009·Analytical and Bioanalytical Chemistry·Leslie R FarrisMelisenda J McDonald

❮ Previous
Next ❯