Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein

Impaired trafficking in a clinical isolate

Leon Caly, Vicky T. Kassouf, Gregory W. Moseley, Russell J. Diefenbach, Anthony L. Cunningham, David A. Jans

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications.
Original languageEnglish
Pages (from-to)735-740
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume470
Issue number3
DOIs
Publication statusPublished - 11 Jan 2016

Keywords

  • viral protein R
  • Vpr
  • dynein
  • DYNLT1
  • nuclear import
  • microtubule

Cite this

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title = "Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein: Impaired trafficking in a clinical isolate",
abstract = "Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications.",
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author = "Leon Caly and Kassouf, {Vicky T.} and Moseley, {Gregory W.} and Diefenbach, {Russell J.} and Cunningham, {Anthony L.} and Jans, {David A.}",
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language = "English",
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journal = "Biochemical and Biophysical Research Communications",
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Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein : Impaired trafficking in a clinical isolate. / Caly, Leon; Kassouf, Vicky T.; Moseley, Gregory W.; Diefenbach, Russell J.; Cunningham, Anthony L.; Jans, David A.

In: Biochemical and Biophysical Research Communications, Vol. 470, No. 3, 11.01.2016, p. 735-740.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Fast track, dynein-dependent nuclear targeting of human immunodeficiency virus Vpr protein

T2 - Impaired trafficking in a clinical isolate

AU - Caly, Leon

AU - Kassouf, Vicky T.

AU - Moseley, Gregory W.

AU - Diefenbach, Russell J.

AU - Cunningham, Anthony L.

AU - Jans, David A.

PY - 2016/1/11

Y1 - 2016/1/11

N2 - Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications.

AB - Nuclear import of the accessory protein Vpr is central to infection by human immunodeficiency virus (HIV). We previously identified the Vpr F72L mutation in a HIV-infected, long-term non-progressor, showing that it resulted in reduced Vpr nuclear accumulation and altered cytoplasmic localisation. Here we demonstrate for the first time that the effects of nuclear accumulation of the F72L mutation are due to impairment of microtubule-dependent-enhancement of Vpr nuclear import. We use high resolution imaging approaches including fluorescence recovery after photobleaching and other approaches to document interaction between Vpr and the dynein light chain protein, DYNLT1, and impaired interaction of the F72L mutant with DYNLT1. The results implicate MTs/DYNLT1 as drivers of Vpr nuclear import and HIV infection, with important therapeutic implications.

KW - viral protein R

KW - Vpr

KW - dynein

KW - DYNLT1

KW - nuclear import

KW - microtubule

UR - http://www.ncbi.nlm.nih.gov/pubmed/26792716

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DO - 10.1016/j.bbrc.2016.01.051

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