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Author Caly, Leon ♦ Kassouf, Vicki T. ♦ Moseley, Gregory W. ♦ Diefenbach, Russell J. ♦ Cunningham, Anthony L. ♦ Jans, David A.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ AIDS VIRUS ♦ BIOMEDICAL RADIOGRAPHY ♦ FLUORESCENCE ♦ MICROTUBULES ♦ MUTANTS ♦ MUTATIONS ♦ PARTICLE TRACKS ♦ PROTEINS
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. - Highlights: • HIV-1 Vpr utilizes the microtubule network to traffic towards the nucleus. • Mechanism relies on interaction between Vpr and dynein light chain protein DYNLT1. • Long-term non-progressor derived mutation (F72L) impairs this interaction. • Key residues in the vicinity of F72 contribute to interaction with DYNLT1.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-02-12
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 470
Issue Number 3


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